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Prediction is very difficult, especially if it's about the future.
Niels Bohr

Introduction

Immune therapy is a safe and effective therapy of diverse cancers. In haematology this efficacy is limited predominately to B-cell lymphoid cancers including acute lymphoblastic leukemia (ALL), lymphomas and plasma cell myeloma. Effective therapies include monoclonal antibodies such as rituximab, antibody-drug conjugates such as brentuximab vedotin, antibody-radionuclide conjugates such as 131-iodine tositumomab, bi-specific monoclonal antibodies (BiTE® antibodies) such as blinatumomab (CD20/CD3) and chimeric antigen receptor T-cells (CAR-T-cells) to CD19, CD20 and to B-cell maturation antigen (BCMA). The target of these immune therapies are B-cell lineage antigens rather than cancer-specific antigens. These interventions are more effective than checkpoint-inhibition directed antibodies such as those to PD-1, or PD-1L or antibodies to CTLA-4 active in solid cancers.

One might expect equal success using immune therapy to treat myeloid cancers such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). However, this is not so. Early attempts to use immunotherapy for AML treatment (with BCG, C.parvum, or leukemia blast antigens) were not successful [1]. At the present time, there is only one FDA-approved therapy of myeloid cancers, gemtuzumab ozogamicin (Myelotarg®) for AML which was first approved >10 years ago, withdrawn and re-approved. Why this discordance?

What are the reasons for successful immune therapy of different blood cancers?

There are two important differences between myeloid and lymphoid cancers. First is the different structures and kinetics of myelopoiesis and lymphopoiesis. Lymphoid and myeloid lineages are divided (dichotomized) at the level of early progenitors. About at 600 billion cells myeloid cells are produced per day in contrast to only about 10 million lymphoid cells per day, a 60-fold difference. Also, granulocytes and platelets survive only a few hours or days in contrast to lymphoid cells which live years. The implication of these differences is a disruption of myelopoiesis is much more serious than a disruption of lymphopoiesis. One be reasonably well without B-cells, somewhat well without T- and NK-cells but you will die immediately without granulocytes and platelets.

Second this the different targetability of myeloid versus lymphoid antigens. As indicated, the target of immune therapy of lymphoid cancers is B-lineage antigens. These antigens are not cancer-specific such that normal B-cells are targeted along with the cancer cells. Fortunately killing all normal B-cells is compatible with life (normal B-cell function can be reversed by giving intravenous immune globulin [IVIG]). In contrast, it is impossible to replace normal granulocyte production, a situation is incompatible with life.

Is there immune surveillance against AML?

Considerable data indicate the immune system is effective in controlling lymphomas. For example, lymphoma-risk is markedly increased in persons with immune deficiency or suppression such as those with severe combined immune deficiency (SCID), acquired immune deficiency syndrome (AIDS) and solid organ and hematopoietic transplant recipients. Most of these lymphomas are Epstein-Barr virus (EBV)-related. However, there is a only a small if any increased risk of AML, CML or myelodysplastic syndrome (MDS) in similar populations and amongst solid organ transplant recipients receiving life-long immune suppression (Fig. 1) [2, 3]. These data imply immune surveillance does not operate effectively against myeloid cancers.

Are there convincing data of an immune response to AML?

Considerable data indicate a strong immune response to myeloid cancers in the setting of a hematopoietic cell transplant. For example, among persons with AML receiving an HLA-identical sibling transplant, cumulative incidence of relapse (CIR) is highest among recipients of a transplant from a genetically-identical twins and lowest among recipients of allotransplants with acute and chronic graft-versus-host disease (GvHD) [4]. This difference correlates with histo-incompatibility between donor and recipient. Graft-versus-host disease (GvHD) and graft-versus-leukemia effect (GvL) may be identical or overlap to different degree in individuals.

Therefore, the answer on targetability of AML immune therapy lies in two considerations: (1) lack of a convincing AML-specific target antigen(s); and (2) unacceptable adverse effects from non-specificity of target antigens used in AML immune therapy such as CD33 and CD124. Therapy against these target antigens can potentially kill AML cells but will unavoidably destroy normal bone marrow cells resulting in death absent a transplant or using synthetic biology techniques.

What is the role of AML-specific antigens in graft-versus-leukaemia (GvL)?

There are several potential targets of anti-AML activity in the context of an allotransplant including: (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens (if they exist). All of these are potential targets of the so-called GvL-effect seen after allotransplants and after donor lymphocyte infusions (DLI). Elsewhere my colleague and I discuss whether this effect is leukemia-specific or against HLA and/or non-HLA antigens and not leukemia-specific [5].

Several variables correlate with success of immune therapy: (1) antigenicity; (2) immunogenicity; (3) accessibility; (4) sensitivity to killing; and (5) collateral damage to normal cells. The major current limitation of these approaches is lack of an AML-specific target antigen. In many models, probability of response to immune therapy correlates with mutation frequency and with estimated numbers of potential cancer-specific neo-antigens [6]. AML cells have an average of 0.28 mutation per megabase of DNA compared with 8.15 mutations for lung cancer, 40-fold less. For this reason checkpoint-inhibitor antibodies and antibodies to CTLA-4 are unlikely to be effective when used alone in persons with AML.

Figure 3. Correlation between coding somatic mutation frequency and objective response rates in diverse cancers [6]

Clinical trials

We can envision any potential immune therapy of blood cancer using along two strategies: antibody therapies and cell therapies. Antibody therapies can be further divided by technology such as unmodified antibodies, antibody-drug conjugates, antibody-radionuclide conjugates (radio-immunotherapy), bi-specific antibodies, and other more advanced techniques [7]. These data are summarized in the Table 1.

An example is gemtuzumab ozogamycin [8]. Clinical trials data are shown in Figure 4.

PD-1 and CTLA-4 inhibitors

Clinical studies of immune checkpoint inhibitors like anti-PD-1 antibodies report little or no benefit. Current studies combine anti-PD-1 antibodies with anti-leukemic drugs [10]. A study in 22 subjects reported complete responses in 4 subjects with extra-medullary relapse of AML but not in subjects with bone marrow relapse [11].

Cell-based immune therapy

Cellular immune therapies use NK-cells and CAR-T- and CAR-NK cells and cytokine-induced NK-cells (CIK). My colleagues and I recently reviewed the current state of cell therapy of AML [12]. We discussed several approaches and concluded that although there are interesting preliminary data, there are no convincing data these approaches are a safe and effective treatment of AML. Perhaps the strongest current data are for NK-cells [13].

Synthetic biology techniques may allow use of anti-CD33 antibodies in AML by using CRISP/Cas9 to edit out CD33 from normal myeloid cells [14].

Conclusions

In summary, immune therapy of AML poses challenges different from immune therapy of lymphoid-lineage cancers. There is progress, for example with gemtuzumab ozogamicin, but major challenges remain. There are potential advantages to immune therapy of AML compared with other cancers such as accessibility of AML cells and susceptibility to killing. However, negative aspects of immune therapy are requirements for antigenicity, immunogenicity, a low mutation rate and unacceptable reduced collateral damage to normal myeloid cells. Whether these challenges can be overcome is unknown. Hopefully so.

References

1. Foon KA, Smalley RV, Riggs CW, Gale RP. The role of immunotherapy in acute myelogenous leukemia. Arch Intern Med 1983;143:1726-1731.
2. Gale RP, Opelz G. Commentary: does immune suppression increase risk of developing acute myeloid leukemia? Leukemia. 2012; 26(3):422-423.
3. Gale RP, Opelz G. Is there immune surveillance against chronic myeloid leukaemia? Possibly, but not much. Leuk Res. 2017;57:109-111.
4. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990;75(3):555-562.
5. Gale RP, Fuchs EJ. Is there really a specific graft-versus-leukaemia effect? Bone Marrow Transplant 2016;51(11): 1413-1415.
6. Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N Engl J Med. 2017; 377(25):2500-2501.
7. Assi R, Kantarjian H, Ravandi F, Daver N. Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors. Curr Opin Hematol. 2018, 25 (2), 136-145.
8. Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamycin in acute myeloid leukemia. Leukemia, 2017; 31(9): 1855-1868.
9. Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab Ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, Phase III ALFA-0701. Trial. 2019;104(1):113-119. doi: 10.3324/haematol.2018.188888.
10. Boddu P, Kantarjian H, Garcia-Manero G, Allison J, Sharma P, Daver N. The emerging role of immune checkpoint based approaches in AML and MDS. Leuk Lymphoma. 2018; 59 (4): 790-802.
11. Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf NR, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016; 375(2):143-153.
12. Hansrivijit P, Gale RP, Barrett J, Ciurea SO. Cellular therapy for acute myeloid leukemia – current status and future prospects. Blood Rev 2019;doi.org/10.1016j. blre.2019.05.002.
13. Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105(8):3051-3057.
14. Kim MY, Yu KR, Kenderian SS, Tsai SO, Dunbar CE, Saar Gill. Genetic inactivation of CD33 in hematopoietic stem cells to enable CAR T Cell immunotherapy for acute myeloid leukemia. Cell 2018;173:1439-1453.

" ["~DETAIL_TEXT"]=> string(13505) "

Prediction is very difficult, especially if it's about the future.
Niels Bohr

Introduction

Immune therapy is a safe and effective therapy of diverse cancers. In haematology this efficacy is limited predominately to B-cell lymphoid cancers including acute lymphoblastic leukemia (ALL), lymphomas and plasma cell myeloma. Effective therapies include monoclonal antibodies such as rituximab, antibody-drug conjugates such as brentuximab vedotin, antibody-radionuclide conjugates such as 131-iodine tositumomab, bi-specific monoclonal antibodies (BiTE® antibodies) such as blinatumomab (CD20/CD3) and chimeric antigen receptor T-cells (CAR-T-cells) to CD19, CD20 and to B-cell maturation antigen (BCMA). The target of these immune therapies are B-cell lineage antigens rather than cancer-specific antigens. These interventions are more effective than checkpoint-inhibition directed antibodies such as those to PD-1, or PD-1L or antibodies to CTLA-4 active in solid cancers.

One might expect equal success using immune therapy to treat myeloid cancers such as acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). However, this is not so. Early attempts to use immunotherapy for AML treatment (with BCG, C.parvum, or leukemia blast antigens) were not successful [1]. At the present time, there is only one FDA-approved therapy of myeloid cancers, gemtuzumab ozogamicin (Myelotarg®) for AML which was first approved >10 years ago, withdrawn and re-approved. Why this discordance?

What are the reasons for successful immune therapy of different blood cancers?

There are two important differences between myeloid and lymphoid cancers. First is the different structures and kinetics of myelopoiesis and lymphopoiesis. Lymphoid and myeloid lineages are divided (dichotomized) at the level of early progenitors. About at 600 billion cells myeloid cells are produced per day in contrast to only about 10 million lymphoid cells per day, a 60-fold difference. Also, granulocytes and platelets survive only a few hours or days in contrast to lymphoid cells which live years. The implication of these differences is a disruption of myelopoiesis is much more serious than a disruption of lymphopoiesis. One be reasonably well without B-cells, somewhat well without T- and NK-cells but you will die immediately without granulocytes and platelets.

Second this the different targetability of myeloid versus lymphoid antigens. As indicated, the target of immune therapy of lymphoid cancers is B-lineage antigens. These antigens are not cancer-specific such that normal B-cells are targeted along with the cancer cells. Fortunately killing all normal B-cells is compatible with life (normal B-cell function can be reversed by giving intravenous immune globulin [IVIG]). In contrast, it is impossible to replace normal granulocyte production, a situation is incompatible with life.

Is there immune surveillance against AML?

Considerable data indicate the immune system is effective in controlling lymphomas. For example, lymphoma-risk is markedly increased in persons with immune deficiency or suppression such as those with severe combined immune deficiency (SCID), acquired immune deficiency syndrome (AIDS) and solid organ and hematopoietic transplant recipients. Most of these lymphomas are Epstein-Barr virus (EBV)-related. However, there is a only a small if any increased risk of AML, CML or myelodysplastic syndrome (MDS) in similar populations and amongst solid organ transplant recipients receiving life-long immune suppression (Fig. 1) [2, 3]. These data imply immune surveillance does not operate effectively against myeloid cancers.

Are there convincing data of an immune response to AML?

Considerable data indicate a strong immune response to myeloid cancers in the setting of a hematopoietic cell transplant. For example, among persons with AML receiving an HLA-identical sibling transplant, cumulative incidence of relapse (CIR) is highest among recipients of a transplant from a genetically-identical twins and lowest among recipients of allotransplants with acute and chronic graft-versus-host disease (GvHD) [4]. This difference correlates with histo-incompatibility between donor and recipient. Graft-versus-host disease (GvHD) and graft-versus-leukemia effect (GvL) may be identical or overlap to different degree in individuals.

Therefore, the answer on targetability of AML immune therapy lies in two considerations: (1) lack of a convincing AML-specific target antigen(s); and (2) unacceptable adverse effects from non-specificity of target antigens used in AML immune therapy such as CD33 and CD124. Therapy against these target antigens can potentially kill AML cells but will unavoidably destroy normal bone marrow cells resulting in death absent a transplant or using synthetic biology techniques.

What is the role of AML-specific antigens in graft-versus-leukaemia (GvL)?

There are several potential targets of anti-AML activity in the context of an allotransplant including: (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens (if they exist). All of these are potential targets of the so-called GvL-effect seen after allotransplants and after donor lymphocyte infusions (DLI). Elsewhere my colleague and I discuss whether this effect is leukemia-specific or against HLA and/or non-HLA antigens and not leukemia-specific [5].

Several variables correlate with success of immune therapy: (1) antigenicity; (2) immunogenicity; (3) accessibility; (4) sensitivity to killing; and (5) collateral damage to normal cells. The major current limitation of these approaches is lack of an AML-specific target antigen. In many models, probability of response to immune therapy correlates with mutation frequency and with estimated numbers of potential cancer-specific neo-antigens [6]. AML cells have an average of 0.28 mutation per megabase of DNA compared with 8.15 mutations for lung cancer, 40-fold less. For this reason checkpoint-inhibitor antibodies and antibodies to CTLA-4 are unlikely to be effective when used alone in persons with AML.

Figure 3. Correlation between coding somatic mutation frequency and objective response rates in diverse cancers [6]

Clinical trials

We can envision any potential immune therapy of blood cancer using along two strategies: antibody therapies and cell therapies. Antibody therapies can be further divided by technology such as unmodified antibodies, antibody-drug conjugates, antibody-radionuclide conjugates (radio-immunotherapy), bi-specific antibodies, and other more advanced techniques [7]. These data are summarized in the Table 1.

An example is gemtuzumab ozogamycin [8]. Clinical trials data are shown in Figure 4.

PD-1 and CTLA-4 inhibitors

Clinical studies of immune checkpoint inhibitors like anti-PD-1 antibodies report little or no benefit. Current studies combine anti-PD-1 antibodies with anti-leukemic drugs [10]. A study in 22 subjects reported complete responses in 4 subjects with extra-medullary relapse of AML but not in subjects with bone marrow relapse [11].

Cell-based immune therapy

Cellular immune therapies use NK-cells and CAR-T- and CAR-NK cells and cytokine-induced NK-cells (CIK). My colleagues and I recently reviewed the current state of cell therapy of AML [12]. We discussed several approaches and concluded that although there are interesting preliminary data, there are no convincing data these approaches are a safe and effective treatment of AML. Perhaps the strongest current data are for NK-cells [13].

Synthetic biology techniques may allow use of anti-CD33 antibodies in AML by using CRISP/Cas9 to edit out CD33 from normal myeloid cells [14].

Conclusions

In summary, immune therapy of AML poses challenges different from immune therapy of lymphoid-lineage cancers. There is progress, for example with gemtuzumab ozogamicin, but major challenges remain. There are potential advantages to immune therapy of AML compared with other cancers such as accessibility of AML cells and susceptibility to killing. However, negative aspects of immune therapy are requirements for antigenicity, immunogenicity, a low mutation rate and unacceptable reduced collateral damage to normal myeloid cells. Whether these challenges can be overcome is unknown. Hopefully so.

References

1. Foon KA, Smalley RV, Riggs CW, Gale RP. The role of immunotherapy in acute myelogenous leukemia. Arch Intern Med 1983;143:1726-1731.
2. Gale RP, Opelz G. Commentary: does immune suppression increase risk of developing acute myeloid leukemia? Leukemia. 2012; 26(3):422-423.
3. Gale RP, Opelz G. Is there immune surveillance against chronic myeloid leukaemia? Possibly, but not much. Leuk Res. 2017;57:109-111.
4. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990;75(3):555-562.
5. Gale RP, Fuchs EJ. Is there really a specific graft-versus-leukaemia effect? Bone Marrow Transplant 2016;51(11): 1413-1415.
6. Yarchoan M, Hopkins A, Jaffee EM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N Engl J Med. 2017; 377(25):2500-2501.
7. Assi R, Kantarjian H, Ravandi F, Daver N. Immune therapies in acute myeloid leukemia: a focus on monoclonal antibodies and immune checkpoint inhibitors. Curr Opin Hematol. 2018, 25 (2), 136-145.
8. Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamycin in acute myeloid leukemia. Leukemia, 2017; 31(9): 1855-1868.
9. Lambert J, Pautas C, Terré C, Raffoux E, Turlure P, Caillot D, Legrand O, Thomas X, Gardin C, Gogat-Marchant K, Rubin SD, Benner RJ, Bousset P, Preudhomme C, Chevret S, Dombret H, Castaigne S. Gemtuzumab Ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, Phase III ALFA-0701. Trial. 2019;104(1):113-119. doi: 10.3324/haematol.2018.188888.
10. Boddu P, Kantarjian H, Garcia-Manero G, Allison J, Sharma P, Daver N. The emerging role of immune checkpoint based approaches in AML and MDS. Leuk Lymphoma. 2018; 59 (4): 790-802.
11. Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf NR, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, et al. Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med. 2016; 375(2):143-153.
12. Hansrivijit P, Gale RP, Barrett J, Ciurea SO. Cellular therapy for acute myeloid leukemia – current status and future prospects. Blood Rev 2019;doi.org/10.1016j. blre.2019.05.002.
13. Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105(8):3051-3057.
14. Kim MY, Yu KR, Kenderian SS, Tsai SO, Dunbar CE, Saar Gill. Genetic inactivation of CD33 in hematopoietic stem cells to enable CAR T Cell immunotherapy for acute myeloid leukemia. Cell 2018;173:1439-1453.

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["ELEMENT_META_KEYWORDS"]=> string(0) "" ["ELEMENT_META_DESCRIPTION"]=> string(164) "Может ли иммунотерапия излечивать острый миелобластный лейкоз?Can immune therapy cure acute myeloid leukemia?" ["ELEMENT_PREVIEW_PICTURE_FILE_ALT"]=> string(3467) "<p style="text-align: justify;">Достигнут значительный прогресс в иммунотерапии различных злокачественных заболеваний. В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.</p> <p style="text-align: justify;">Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. 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Гэйл</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(32) "

Роберт П. Гэйл

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Центр гематологических исследований, отдел иммунологии и воспаления, Имперский колледж Лондона, Великобритания

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "26439" ["VALUE"]=> array(2) { ["TEXT"]=> string(3467) "<p style="text-align: justify;">Достигнут значительный прогресс в иммунотерапии различных злокачественных заболеваний. В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.</p> <p style="text-align: justify;">Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ. </p> <h2>Ключевые слова</h2> <p style="text-align: justify;">Острый миелобластный лейкоз, мутации, неоантигены, иммунотерапия.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3389) "

Достигнут значительный прогресс в иммунотерапии различных злокачественных заболеваний. В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.

Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ.

Ключевые слова

Острый миелобластный лейкоз, мутации, неоантигены, иммунотерапия.

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Robert P. Gale

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Imperial College London, London, UK

Correspondence
Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, Visiting Professor Haematology, Centre for Haematology Research, Department of Immunology and Inflammation Imperial College London, London, UK
E-mail: robertpetergale@gmail.com

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There is considerable progress in immune therapy of diverse cancers. In haematology these advances are mostly limited to lymphoid cancers. Effective therapies include monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells to lymphoid lineage-antigens such as CD19, CD20 and B-cell maturation antigen (BCMA). Gemtuzumab ozogamicin (Myelotarg®) is the only FDA-approved immune-based therapy for acute myeloid leukemia (AML). Several clinical trials of antibodies to CD38 and CD123 are reported with unimpressive efficacy and safety concerns. Reasons are higher daily production rates of myeloid cells and unacceptable collateral damage to normal haematopoietic cells because of imperfect specificity for AML cells. Potential targets of anti-AML immune therapy are (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens. Data supporting an effective allogeneic anti-AML effect come from studies in recipients of haematopoietic cell transplants with graft-versus-host disease (GvHD) and recipients of donor lymphocyte infusions (DLI). A special problem is a relative paucity of neo-antigens in AML compared with solid cancers because of a low cumulative mutation frequency. Cell immune therapy trials are in progress including CAR-T-cells, CAR-NK-cells and allogeneic NK-cells. Approaches using synthetic biology are being developed. Presently, except for gemtuzumab ozogamicin there are no convincing data of efficacy of immune therapy in AML.

Keywords

Acute myeloid leukemia, mutations, neoantigens, immune therapy.

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Robert P. Gale

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Robert P. Gale

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There is considerable progress in immune therapy of diverse cancers. In haematology these advances are mostly limited to lymphoid cancers. Effective therapies include monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells to lymphoid lineage-antigens such as CD19, CD20 and B-cell maturation antigen (BCMA). Gemtuzumab ozogamicin (Myelotarg®) is the only FDA-approved immune-based therapy for acute myeloid leukemia (AML). Several clinical trials of antibodies to CD38 and CD123 are reported with unimpressive efficacy and safety concerns. Reasons are higher daily production rates of myeloid cells and unacceptable collateral damage to normal haematopoietic cells because of imperfect specificity for AML cells. Potential targets of anti-AML immune therapy are (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens. Data supporting an effective allogeneic anti-AML effect come from studies in recipients of haematopoietic cell transplants with graft-versus-host disease (GvHD) and recipients of donor lymphocyte infusions (DLI). A special problem is a relative paucity of neo-antigens in AML compared with solid cancers because of a low cumulative mutation frequency. Cell immune therapy trials are in progress including CAR-T-cells, CAR-NK-cells and allogeneic NK-cells. Approaches using synthetic biology are being developed. Presently, except for gemtuzumab ozogamicin there are no convincing data of efficacy of immune therapy in AML.

Keywords

Acute myeloid leukemia, mutations, neoantigens, immune therapy.

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There is considerable progress in immune therapy of diverse cancers. In haematology these advances are mostly limited to lymphoid cancers. Effective therapies include monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells to lymphoid lineage-antigens such as CD19, CD20 and B-cell maturation antigen (BCMA). Gemtuzumab ozogamicin (Myelotarg®) is the only FDA-approved immune-based therapy for acute myeloid leukemia (AML). Several clinical trials of antibodies to CD38 and CD123 are reported with unimpressive efficacy and safety concerns. Reasons are higher daily production rates of myeloid cells and unacceptable collateral damage to normal haematopoietic cells because of imperfect specificity for AML cells. Potential targets of anti-AML immune therapy are (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens. Data supporting an effective allogeneic anti-AML effect come from studies in recipients of haematopoietic cell transplants with graft-versus-host disease (GvHD) and recipients of donor lymphocyte infusions (DLI). A special problem is a relative paucity of neo-antigens in AML compared with solid cancers because of a low cumulative mutation frequency. Cell immune therapy trials are in progress including CAR-T-cells, CAR-NK-cells and allogeneic NK-cells. Approaches using synthetic biology are being developed. Presently, except for gemtuzumab ozogamicin there are no convincing data of efficacy of immune therapy in AML.

Keywords

Acute myeloid leukemia, mutations, neoantigens, immune therapy.

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Imperial College London, London, UK

Correspondence
Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, Visiting Professor Haematology, Centre for Haematology Research, Department of Immunology and Inflammation Imperial College London, London, UK
E-mail: robertpetergale@gmail.com

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Imperial College London, London, UK

Correspondence
Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, Visiting Professor Haematology, Centre for Haematology Research, Department of Immunology and Inflammation Imperial College London, London, UK
E-mail: robertpetergale@gmail.com

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Роберт П. Гэйл

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Роберт П. Гэйл

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В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.</p> <p style="text-align: justify;">Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ. </p> <h2>Ключевые слова</h2> <p style="text-align: justify;">Острый миелобластный лейкоз, мутации, неоантигены, иммунотерапия.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(3389) "

Достигнут значительный прогресс в иммунотерапии различных злокачественных заболеваний. В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.

Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ.

Ключевые слова

Острый миелобластный лейкоз, мутации, неоантигены, иммунотерапия.

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Достигнут значительный прогресс в иммунотерапии различных злокачественных заболеваний. В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.

Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ.

Ключевые слова

Острый миелобластный лейкоз, мутации, неоантигены, иммунотерапия.

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Центр гематологических исследований, отдел иммунологии и воспаления, Имперский колледж Лондона, Великобритания

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Центр гематологических исследований, отдел иммунологии и воспаления, Имперский колледж Лондона, Великобритания

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Introduction

Target drug delivery systems find increasingly wide application in medicine. Use of these systems requires high stability of encapsulated MC, low dosage and toxicity, prolonged therapeutic action. Porous vaterites (one of three calcium carbonate polymorphs) have been used as carriers in delivery systems (DS) for biologically active compounds and medicinal compounds since 2004 [1]. In many research works, they were used as "sacrificed" matrices. Porous carbonate cores were saturated with biologically active compounds using different methods, then their surface was coated layer-by-layer with polyelectrolytes; polymers with opposite excess charges were applied by turns. After dissolution of СаСО₃ cores in the presence of chelate compounds (e.g., ethylenediaminetetraacetic acid), these multilayered shells were used as capsules for delivery of biologically active compounds [2]. In some cases, carbonate cores were not dissolved, but used together with their PE shells [3-5]. Since one of the objectives of employing delivery systems is to provide prolonged release of an encapsulated MC, preservation of the porous core increases resistance of the structure against external influence and thus helps attain this goal. Another way of using СаСО₃ as a component of DS consists in including carbonate cores into alginate granule, which significantly simplifies DS preparation [6].

A number of research papers [7-9] report preparation of DS with СаСО₃ in combination with various polymers; antitumor drug doxorubicin was used as an active substance. In vitro experiments demonstrated prolonged pH-dependent release of the drug.

Note that synthesis of СаСО₃ cores is relatively simple. It is believed that they are completely biocompatible and biodegradable; they show neither toxicity nor immunogenicity, and thus are well tolerated by a recipient organism [10]. This opinion was confirmed by the studies of behavior of СаСО₃-based delivery systems in various model environments as well as upon administration of these DS into living rabbits, rats and mice by various methods. Configurations of DS based on СаСО₃ cores depend on the method used for their administration. The influence of various environments on the DS containing СаСО₃ cores is described in the papers that are quoted below.

In water or physiological solution (0.9% NaCl), СаСО₃ vaterites undergo morphological transformations [11]. At medium temperatures, porous vaterites turn into calcites (which are more thermodynamically stable), and at elevated temperatures (above 37-40°С), they are transformed into aragonites [12]. Since these polymorphs are not porous, recrystallization is accompanied by release of drugs encapsulated in vaterites. The drug release profiles correlate with percentages of calcites formed [13].

Oral administration is the most convenient method for patients. However, vaterite cores dissolve in acidic medium of a stomach; therefore, the cores with encapsulated MC should be protected. This protection can be provided both by PE shells (on condition that their components are stable in acidic stomach environment) and alginate granules surrounding СаСО₃ cores. Since it is necessary to provide penetration of MC from intestinal tract into main blood flow, a polymer shell should swell or dissolve in the middle division of intestinal tract, thus releasing СаСО₃ with MC. Model experiments involving 0.15 M phosphate buffer with рН=7.4 (model intestinal fluid) demonstrated that CaCO3 enters into ion-exchange reaction with phosphate ions; as a result, rather compact porous vaterites are transformed into loose macroporous СаНРО₄ structures. This process facilitates release of the encapsulated MC. Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) studies revealed structural changes in СаСО₃ vaterites [14]. Similar transformation also occurs with time in the case of two-level DS that consist of alginate granules and carbonate cores. The presence of fragments of СаСО₃ cores in blood and plasma of experimental animals (rats) was confirmed by elemental analysis of the samples [15].

The requirements for size of DS intended for parentheral administration are more rigid, but in this case the carrier should not be necessary protected (unlike the systems used in oral delivery). The СаСО₃ vaterites that were synthesized according to the technique described in [1] have sizes of 3-5 μm. Diameter of cores may be reduced by various methods: change in the basic synthesis conditions – increasing concentration of the initial solutions of salts (Na₂CO₃ and CaCl₂), and stirring intensity [16]; increase in viscosity of starting solutions by adding ethylene glycol [17]; addition of a polyelectrolyte during co-precipitation of the salts [18-20]. Unfortunately, the latter method gives low yield of the final product and requires monitoring interaction between MC and polymer.

The authors of [21] used intratracheal administration of СаСО₃ cores that contained BSA protein labeled with Cy7 fluorophore. It was demonstrated that efficiency of penetration into lungs for carriers of various diameters decreased with increasing core size from 0.65 to 3.15 μm. Penetration of the labeled protein into lungs with the aid of СаСО₃ vaterites of different sizes was confirmed by confocal microscopy of mouse lung cryocut sections. The lower DS size, the deeper they penetrate into lung tissue. Confocal microscopy makes it possible to localize СаСО₃ carriers in a sample. Recrystallization of vaterites was observed in the model environment that included physiological solution and bronchoalveolar lavage (containing proteins and surfactants). It was shown that the components of lavage covering vaterite surface protect them from recrystallization.

The authors of [22] demonstrated possibility of penetration of СаСО₃ vaterites with encapsulated loperamide through blood-brain barrier of rats after intranasal administration. In order to enhance mucoadhesion, СаСО₃ cores were covered with mucoadhesive polymers (hyaluronic acid or poly-L-lysine).

It was suggested [10] to use СаСО₃ cores with encapsulated superoxide dismutase enzyme as an ophthalmic delivery system. According to the authors, no undesirable effects were observed after injections of vaterite microcrystals (concentration 10 mg/mL) into eye tissues of rabbits.

In vivo transdermal administration of СаСО₃ particles (diameter: 4 μm) to a depth of 200 μm was performed via laser ablation followed by massage. These relatively large particles did not penetrate into the underlying derma. In 1 week after beginning of the experiment, СаСО₃ particles dissolved in rat body and released the encapsulated compound [23].

It was revealed [24] that porous СаСО₃ cores degraded completely in three months after introducing them into rat bone tissue.

Along with other calcium-containing inorganic nanostructured materials, СаСО₃ vaterites find increasing applications in regenerative medicine and tissue engineering [25].

To summarize, all methods for introducing DS based on СаСО₃ vaterites are aimed at providing absorption of cores by cells. The influence of size and shape of СаСО₃ particles on cell uptake was studied in [26]. It was demonstrated that internalization is more effective for spherical particles with the lowest volume, and for elongated particles.

Currently, there are no literature data on the studies of behavior of vaterite-based DS in human blood plasma and upon their intramuscular administration. When using the majority of the above-mentioned methods, it is necessary to study transformations of DS in blood plasma. The second method may be efficient when DS with MC are introduced directly into tumor tissue. Thus, the goal of the present work was to study behavior of spherical СаСО₃ vaterites (components of target delivery systems for antitumor drugs) in vitro (in human blood plasma) and in vivo (in rat muscle tissue).

Abbreviations: DS, delivery systems; MC, medicinal compounds; EDS, energy dispersive spectroscopy; SEM, scanning electron microscopy; EDTA, ethylenediaminetetraacetic acid; BSA, bovine serum albumin.

Materials and methods

Synthesis of carbonate cores

Porous vaterites (СаСО₃ cores) were prepared by co-precipitation according to the technique described in [1] with some modifications. Equal volumes of 1 M aqueous solutions of CaCl₂×2H₂O and Na₂CO₃ were rapidly mixed at stirring with an RW 20 anchor-type mechanical stirrer (Kika-Werk, Switzerland) (1000 rpm). The mixture was stirred for 30 s. Then the suspension was filtered through Schott filter glass (#16), washed thrice with distilled water, then with acetone/water mixtures with increasing acetone concentrations (33%, 50%, and 100%). The precipitate was dried in thermostat at 40-50°C until a constant weight was achieved. Diameter of the obtained cores varies from 1 to 3 μm.

Interaction between СаСО₃ and human blood plasma

Interaction between carbonate cores and human blood plasma was performed at continuous stirring of the suspension. When the reaction was complete, the cores were centrifuged (5 min at 3000 rpm); the supernatant was poured out and substituted for distilled water. The procedure was performed twice. The cores were dried at 40°C until a constant weight was achieved.

Scanning electron microscopy (SEM)

SEM microphotographs of СаСО₃ cores were obtained with the help of a Supra 55VP scanning electron microscope (Carl Zeiss, Germany) using secondary electron imaging; before the experiments, the samples were coated with thin platinum layer.

Energy dispersive spectroscopy (EDS)

Elemental compositions of the samples were determined by energy-dispersive spectroscopy (EDS) using an X-Max 80 detector (Oxford Instruments, UK).

Experiments with animals

The experiments involving animals were performed according to the laboratory animal welfare policy accepted in Russian Federation and European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123, Strasbourg, 1986).

In vivo experiments involved 10 male Wistar rats (weight: 200-250 g, age: 3 months). Before studies of bioresorption in vivo, СаСО₃ cores were sterilized in autoclave at 110°С for 1 h. Each weighed amount of СаСО₃ (10 mg) intended for an experiment in each of two locations in one animal was carefully hermetically packed in aluminum foil. The animals were operated under general anesthesia (intraperitoneal injections of Zoletil 100 (0.1 mL) and Rometar (20 mg/mL) solutions, 0.0125 mL per 0.1 kg of animal body mass). The samples were placed into thigh great adductor muscles (musculus adductor magnus) of both hind extremities. Then the wounds were sutured layer by layer using atraumatic needles and Prolene 4-0 suture. After outer suturing, the rats were caged individually, were fed standard diet, and had free access to water. All animals were active after surgery; no inflammation in the implantation area was observed, which is indicative of the absence of detrimental effects of implantation.

Histological studies

In 1 and 2 weeks after operation, samples of muscle tissue containing СаСО₃ were fixed with 10% neutral formalin in phosphate buffer (рН=7.4) for not less than 24 hrs, dehydrated using a series of ethanol solutions with increasing concentrations, and enclosed in paraffin blocks according to the standard histological technique. The paraffin cuts (5 μm in width) transverse to muscular fibers were obtained with the use of an Accu-Cut SRT 200 microtome (Sakura, Japan) and stained with Mayer hematoxylin and eosin (Bio-Optica, Italy). The connective tissue was visualized according to the Mallory method (BioVitrum, Russia). Microscopic analysis was performed using a Leica DM750 light microscope (Germany) with a 10× ocular and 4, 10, 40, and 100× objectives. Images were recorded with an ICC50 camera (Leica, Germany).

Results

Influence of human blood plasma on the structure of СаСО₃ cores

Blood plasma contains phosphate ions, which enter into reaction with СаСО₃ vaterites; as a result, macroporous СаНРО₄ structures are gradually formed [14]. It is seen in the SEM images of СаСО₃ vaterites (Fig. 1) that the objects with increasingly loose structure are formed with time; they consist of needle-like subunits less than 1 μm in diameter.

Phosphorus content in the studied structures was determined by energy-dispersive spectroscopy (see Table 1).

The EDS data show that phosphorus content in transformed structures increases with time; this result confirms that ion exchange reaction indeed occurs in СаСО₃ vaterites.

Figure 1. Microphotographs of СаСО₃ vaterites taken upon interaction with human blood plasma for various periods of time: A – 2 hrs; B – 24 hrs; C – 50 hrs

Transformation of СаСО₃ vaterites upon intramuscular administration

After injection of СаСО₃ vaterites into thigh great adductor muscles (musculus adductor magnus) of both hind extremities in rats, needle-like structures were formed (Fig. 2) and then gradually disappeared in two weeks due to bioresorption. Presumably, these needles are aragonites (one of three СаСО₃ polymorphs). Fig. 2B presents the magnified image of the area where vaterites were introduced and then transformed into aragonites (1 week after operation). As was mentioned in Introduction, aragonites (non-porous elongated structures) are one of three morphological modifications of calcium carbonate, along with non-porous (usually cubic) calcites and porous spherical vaterites (which are used as components of target drug delivery systems). Transformation of vaterites during their use in delivery systems into calcites is frequently observed [13]. Formation of aragonite-like structures in the process of bioresorption of СаСО₃ vaterites was revealed in the present work for the first time.

Figure 2. Histological cuts of rat muscle tissue obtained in 1 week after implantation of СаСО₃ vaterites. Staining with hematoxylin and eosin; objectives 10× (а), 40× (b)

Discussion

he reason for transformation of porous СаСО₃ vaterites (diameter: 1 – 3 μm) into needle-like aragonites (length: 30 – 150 μm, width: 10 – 40 μm) in muscle tissue still remains unclear. It may be suggested that morphological transformation of vaterites is influenced by the following factors. First, there is a difference between pH values of muscle tissue and blood or its components (pH of muscle tissue is lower). The second factor involves peculiarities of metabolic processes, mainly, exchange of carbon dioxide. Upon interaction with water, carbon dioxide forms carbonic acid, which reacts with calcium carbonate. Among other factors are intensive action of immune cells, and, finally, mechanic action related to muscle contraction. This issue should be investigated further.

The comparison between our results and the literature data on transformation of СаСО₃ vaterites with encapsulated Fe₃O₄ nanoparticles (which occurred after shallow transdermal injection into rat body [23]) shows that no vaterite modification in muscle tissue was observed. The histological sections prepared in one week after transdermal administration show spherical structures almost similar to the initial cores. In two weeks after operation, vaterites underwent bioresorption, and Fe₃O₄ nanoparticles were released. These data may indirectly confirm our hypothesis concerning the influence of the above factors on transformation of CaCO₃ vaterites in muscle tissue.

Bioresorption of vaterites in blood plasma in vitro is also completed in relatively short period of time (several weeks), while plasma composition remains mostly unchanged.

The main advantage of the DS based on CaCO₃ vaterites intended for intramuscular administration of antitumor preparations is the fact that modified carbonate cores undergo complete bioresorption in 2 weeks in vivo and exert no negative influence on the surrounding tissues. The fact that aragonites are formed in the muscles once again indicates the ambiguity of applying the conclusions obtained from in vitro experiments to the in vivo behavior of the studied objects.

The obtained results confirm ability of porous calcium carbonate cores for bioresorption and their safety for medicinal use, which allows us to recommend porous CaCO₃ vaterites for further experimental studies as components of target drug delivery systems.

Conflict of interests

None declared.

References

1. Volodkin DV, Petrov AI, Prevot M, Sukhorukov GB. Matrix polyelectrolyte microcapsules: new system for macromolecule encapsulation. Langmuir. 2004; 20: 3398-3406.
2. She Z, Wang CX, Li J, Sukhorukov GB, Antipina MN. Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer microcapsules and its controlled release for enhancing cell proliferation. Biomacromolecules. 2012; 13(7): 2174-2180. DOI: 10.1021/bm3005879.
3. Liu D, Jiang G, Yu W, Tong Z, Kong X, Yao J. Oral delivery of insulin using CaCO3-based composite nanocarriers with hyaluronic acid coatings. Materials Letters. 2017; 188: 263-266. DOI: 10.1016/j.matlet.2016.10.117.
4. Ramalapaa B, Crasson O, Vandevenne M, Cordonnier T, Galleni M, Boury F. Protein-polysaccharide complexes for enhanced protein delivery in hyaluronic acid templated calcium carbonate microparticles. J Mater Chem B. 2017; 5: 7360-7368. DOI: 10.1039/C7TB01538K.
5. Peng C, Zhao Q, Gao C. Sustained delivery of doxorubicin by porous CaCO3 and chitosan/alginate multilayers-coated CaCO3 microparticles. Colloids and Surfaces A: Physicochem Eng Aspects. 2010; 353:132–139. DOI:10.1016/j.colsurfa.2009.11.004.
6. Sudareva N, Suvorova O, Saprykina N, Vilesov A, Bel’tyukov P, Petunov S. Alginate-containing systems for oral delivery of superoxide dismutase. Comparison of various configurations and their properties. J Microencapsulation. 2016; 33(5): 487-496. DOI: 10.1080/02652048.2016.1206146.
7. Zhao D, Zhuo R, Cheng S. Alginate modified nanostructured calcium carbonate with enhanced delivery efficiency for gene and drug delivery. Mol BioSystems. 2012; 8: 753-759. DOI: 10.1039/c1mb05337j.
8. Liang P, Liu C, Zhuo R, Cheng S. Self-assembled inorganic/organic hybrid nanoparticles with multi-functionalized surfaces for active targeting drug delivery. J Mat Chem B. 2013; 1: 4243-4250. DOI: 10.1039/C3TB20455C.
9. Trushina DB, Akasov RA, Khovankina AV, Borodina TN, Bukreeva TV, Markvicheva EA. Doxorubicin-loaded biodegradable capsules: Temperature induced shrinking and study of cytotoxicity in vitro. J Mol Liquids. 2019; 284: 15215-224. DOI: 10.1016/j.molliq.2019.03.152.
10. Binevski PV, Balabushevich NG, Uvarova VI, Vikulina AS, Volodkin D. Bio-friendly encapsulation of superoxide dismutase into vaterite CaCO3 crystals. Enzyme activity, release mechanism, and perspectives for ophthalmology. Colloids and Surfaces B: Biointerfaces. 2019; 181: 437-449. DOI: 10.1016/j.colsurfb.2019.05.077.
11. Parakhonskiy B, Tessarolo F, Haase A, Antolini R. Dependence of sub-micron vaterite container release properties on pH and ionic strength of the surrounding solution. Adv Sci Technology. 2013; 86: 81-85. DOI: 10.4028/www.scientific. net/AST.86.81.
12. Ogino T, Suzuki T, Sawada K. The formation and transformation mechanism of calcium carbonate in water. Geochim Cosmochim Acta. 1987; 51(10): 2757-2767.
13. Sergeeva A, Sergeev R, Lengert E, Zakharevich A, Parakhonskiy B, Gorin D, Sergeev S, Volodkin D. Composite magnetite and protein containing CaCO3 crystals. External manipulation and vaterites-calcite recrystallization-mediated release performance. ACS Appl Mater Interfaces. 2015; 7:21315-21325. DOI: 10.1021/acsami. 5b05848.
14. Sudareva NN, Saprykina NN, Popova EV, Vilesov AD. Porous calcium carbonate cores as templates for preparation of peroral proteins delivery systems. The influence of composition of simulated gastrointestinal fluids on the structure and morphology of carbonate cores. Chapter 4. In: "Calcium Carbonate: Occurrence, Characterization and Applications". (Ed. A.Cohen), Nova Science Publishers, Inc (NOVA). 2015, pp.73-95.
15. Sudareva N, Suvorova O, Saprykina N, Smirnova N, Bel'tiukov P, Petunov S, Radilov А, Vilesov A. Two-level delivery systems based on CaCO₃ cores for oral administration of therapeutic peptides. J Microencapsulation. 2018; 35: 619-634. DOI:10.1080/02652048.2018.155924.
16. Sudareva N, Popova H, Saprykina N, Bronnikov S. Structural optimization of calcium carbonate cores as templates for protein encapsulation. J Microencapsulation. 2014; 3(14): 333-343. DOI: 10.3109/02652048.2013.858788.
17. Parakhonskiy BV, Haase A, Antolini R. Sub-micrometer vaterites containers: synthesis, substance loading, and release. Angew Chem Int. Edition. 2012; 51: 1195-1197.
18. Zou Z, Bertinetti L, Politi Y, Fratzl P, Habraken WJ. Control of polymorph selection in amorphous calcium carbonate crystallization by poly(aspartic acid): two different mechanisms. Small. 2017; 13:1603100. DOI: 10.1002/smll.201603100.
19. Nagaraja AT, Pradhan S, McShane MJ. Poly(vinylsulfonic acid) assisted synthesis of aqueous solution stable vaterite calcium carbonate nanoparticles. J Colloid Interface Sci. 2014; 418: 366-372.
20. Zhao D, Zhuo R, Cheng S. Alginate modified nanostructured calcium carbonate with enhanced delivery efficiency for gene and drug delivery. Mol Biosystems. 2012; 8:753-759.
21. Gusliakova O, Atochina-Vasserman EN, Sindeeva O, Sindeev S, Pinyaev S, Pyataev N, Revin V, Sukhorukov GB, Gorin D, Gow AJ. Use of submicron vaterite particles serves as an effective delivery vehicle to the respiratory portion of the lung. Front Pharmacol: Exp Pharmacol and Drug Discovery. 2018; 9: Article 559. DOI: 10.3389/fphar.2018.00559.
22. Borodina, TN, Trushina DB, Marchenko IV, Bukreeva TV. Calcium carbonate-based mucoadhesive microcontainers for intranasal delivery of drugs bypassing the blood-brain barrier. BioNanoScience. 2016; 6: 261-268. DOI: 10.1007/s12668-016-0212-2.
23. Genina EA, Svenskaya YI, Yanina IY, Dolotov LE, Navolokin NA, Bashkatov AN, Terentyuk GS, Bucharskaya AB, Maslyakova GN, Gorin DA, Tuchin VV, Sukhorukov GB. In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers. Biomed Opt Express. 2016; 7: 2082-2087. DOI: 10.1364/BOE.7.002082.
24. Ohgushi H, Okumura M, Yoshikawa T, Inboue K, Senpuku N, Tamai S, Shors EC. Bone formation process in porous calcium carbonate and hydroxyapatite. J Biomed Mater Res. 1992; 26 (7): 885-895. DOI: 10.1002/jbm.820260705.
25. Trushina DB, Bukreeva TV, Kovalchuk MV, Antipina MN. CaCO3 vaterite microparticles for biomedical and personal care applications. Materials Sci Engineering C. 2014; 45: 644-658. DOI: 10.1016/j.msec.2014.04.050.
26. Parakhonskiy B, Zyuzin MV, Yashchenok A, Carregal-Romero S, Rejman J, Möhwald H. The influence of the size and aspect ratio of anisotropic, porous CaCO₃ particles on their uptake by cells. J Nanobiotechnol. 2015; 13: Article 53. doi: 10.1186/s12951-015-0111-7.

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Introduction

Target drug delivery systems find increasingly wide application in medicine. Use of these systems requires high stability of encapsulated MC, low dosage and toxicity, prolonged therapeutic action. Porous vaterites (one of three calcium carbonate polymorphs) have been used as carriers in delivery systems (DS) for biologically active compounds and medicinal compounds since 2004 [1]. In many research works, they were used as "sacrificed" matrices. Porous carbonate cores were saturated with biologically active compounds using different methods, then their surface was coated layer-by-layer with polyelectrolytes; polymers with opposite excess charges were applied by turns. After dissolution of СаСО₃ cores in the presence of chelate compounds (e.g., ethylenediaminetetraacetic acid), these multilayered shells were used as capsules for delivery of biologically active compounds [2]. In some cases, carbonate cores were not dissolved, but used together with their PE shells [3-5]. Since one of the objectives of employing delivery systems is to provide prolonged release of an encapsulated MC, preservation of the porous core increases resistance of the structure against external influence and thus helps attain this goal. Another way of using СаСО₃ as a component of DS consists in including carbonate cores into alginate granule, which significantly simplifies DS preparation [6].

A number of research papers [7-9] report preparation of DS with СаСО₃ in combination with various polymers; antitumor drug doxorubicin was used as an active substance. In vitro experiments demonstrated prolonged pH-dependent release of the drug.

Note that synthesis of СаСО₃ cores is relatively simple. It is believed that they are completely biocompatible and biodegradable; they show neither toxicity nor immunogenicity, and thus are well tolerated by a recipient organism [10]. This opinion was confirmed by the studies of behavior of СаСО₃-based delivery systems in various model environments as well as upon administration of these DS into living rabbits, rats and mice by various methods. Configurations of DS based on СаСО₃ cores depend on the method used for their administration. The influence of various environments on the DS containing СаСО₃ cores is described in the papers that are quoted below.

In water or physiological solution (0.9% NaCl), СаСО₃ vaterites undergo morphological transformations [11]. At medium temperatures, porous vaterites turn into calcites (which are more thermodynamically stable), and at elevated temperatures (above 37-40°С), they are transformed into aragonites [12]. Since these polymorphs are not porous, recrystallization is accompanied by release of drugs encapsulated in vaterites. The drug release profiles correlate with percentages of calcites formed [13].

Oral administration is the most convenient method for patients. However, vaterite cores dissolve in acidic medium of a stomach; therefore, the cores with encapsulated MC should be protected. This protection can be provided both by PE shells (on condition that their components are stable in acidic stomach environment) and alginate granules surrounding СаСО₃ cores. Since it is necessary to provide penetration of MC from intestinal tract into main blood flow, a polymer shell should swell or dissolve in the middle division of intestinal tract, thus releasing СаСО₃ with MC. Model experiments involving 0.15 M phosphate buffer with рН=7.4 (model intestinal fluid) demonstrated that CaCO3 enters into ion-exchange reaction with phosphate ions; as a result, rather compact porous vaterites are transformed into loose macroporous СаНРО₄ structures. This process facilitates release of the encapsulated MC. Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) studies revealed structural changes in СаСО₃ vaterites [14]. Similar transformation also occurs with time in the case of two-level DS that consist of alginate granules and carbonate cores. The presence of fragments of СаСО₃ cores in blood and plasma of experimental animals (rats) was confirmed by elemental analysis of the samples [15].

The requirements for size of DS intended for parentheral administration are more rigid, but in this case the carrier should not be necessary protected (unlike the systems used in oral delivery). The СаСО₃ vaterites that were synthesized according to the technique described in [1] have sizes of 3-5 μm. Diameter of cores may be reduced by various methods: change in the basic synthesis conditions – increasing concentration of the initial solutions of salts (Na₂CO₃ and CaCl₂), and stirring intensity [16]; increase in viscosity of starting solutions by adding ethylene glycol [17]; addition of a polyelectrolyte during co-precipitation of the salts [18-20]. Unfortunately, the latter method gives low yield of the final product and requires monitoring interaction between MC and polymer.

The authors of [21] used intratracheal administration of СаСО₃ cores that contained BSA protein labeled with Cy7 fluorophore. It was demonstrated that efficiency of penetration into lungs for carriers of various diameters decreased with increasing core size from 0.65 to 3.15 μm. Penetration of the labeled protein into lungs with the aid of СаСО₃ vaterites of different sizes was confirmed by confocal microscopy of mouse lung cryocut sections. The lower DS size, the deeper they penetrate into lung tissue. Confocal microscopy makes it possible to localize СаСО₃ carriers in a sample. Recrystallization of vaterites was observed in the model environment that included physiological solution and bronchoalveolar lavage (containing proteins and surfactants). It was shown that the components of lavage covering vaterite surface protect them from recrystallization.

The authors of [22] demonstrated possibility of penetration of СаСО₃ vaterites with encapsulated loperamide through blood-brain barrier of rats after intranasal administration. In order to enhance mucoadhesion, СаСО₃ cores were covered with mucoadhesive polymers (hyaluronic acid or poly-L-lysine).

It was suggested [10] to use СаСО₃ cores with encapsulated superoxide dismutase enzyme as an ophthalmic delivery system. According to the authors, no undesirable effects were observed after injections of vaterite microcrystals (concentration 10 mg/mL) into eye tissues of rabbits.

In vivo transdermal administration of СаСО₃ particles (diameter: 4 μm) to a depth of 200 μm was performed via laser ablation followed by massage. These relatively large particles did not penetrate into the underlying derma. In 1 week after beginning of the experiment, СаСО₃ particles dissolved in rat body and released the encapsulated compound [23].

It was revealed [24] that porous СаСО₃ cores degraded completely in three months after introducing them into rat bone tissue.

Along with other calcium-containing inorganic nanostructured materials, СаСО₃ vaterites find increasing applications in regenerative medicine and tissue engineering [25].

To summarize, all methods for introducing DS based on СаСО₃ vaterites are aimed at providing absorption of cores by cells. The influence of size and shape of СаСО₃ particles on cell uptake was studied in [26]. It was demonstrated that internalization is more effective for spherical particles with the lowest volume, and for elongated particles.

Currently, there are no literature data on the studies of behavior of vaterite-based DS in human blood plasma and upon their intramuscular administration. When using the majority of the above-mentioned methods, it is necessary to study transformations of DS in blood plasma. The second method may be efficient when DS with MC are introduced directly into tumor tissue. Thus, the goal of the present work was to study behavior of spherical СаСО₃ vaterites (components of target delivery systems for antitumor drugs) in vitro (in human blood plasma) and in vivo (in rat muscle tissue).

Abbreviations: DS, delivery systems; MC, medicinal compounds; EDS, energy dispersive spectroscopy; SEM, scanning electron microscopy; EDTA, ethylenediaminetetraacetic acid; BSA, bovine serum albumin.

Materials and methods

Synthesis of carbonate cores

Porous vaterites (СаСО₃ cores) were prepared by co-precipitation according to the technique described in [1] with some modifications. Equal volumes of 1 M aqueous solutions of CaCl₂×2H₂O and Na₂CO₃ were rapidly mixed at stirring with an RW 20 anchor-type mechanical stirrer (Kika-Werk, Switzerland) (1000 rpm). The mixture was stirred for 30 s. Then the suspension was filtered through Schott filter glass (#16), washed thrice with distilled water, then with acetone/water mixtures with increasing acetone concentrations (33%, 50%, and 100%). The precipitate was dried in thermostat at 40-50°C until a constant weight was achieved. Diameter of the obtained cores varies from 1 to 3 μm.

Interaction between СаСО₃ and human blood plasma

Interaction between carbonate cores and human blood plasma was performed at continuous stirring of the suspension. When the reaction was complete, the cores were centrifuged (5 min at 3000 rpm); the supernatant was poured out and substituted for distilled water. The procedure was performed twice. The cores were dried at 40°C until a constant weight was achieved.

Scanning electron microscopy (SEM)

SEM microphotographs of СаСО₃ cores were obtained with the help of a Supra 55VP scanning electron microscope (Carl Zeiss, Germany) using secondary electron imaging; before the experiments, the samples were coated with thin platinum layer.

Energy dispersive spectroscopy (EDS)

Elemental compositions of the samples were determined by energy-dispersive spectroscopy (EDS) using an X-Max 80 detector (Oxford Instruments, UK).

Experiments with animals

The experiments involving animals were performed according to the laboratory animal welfare policy accepted in Russian Federation and European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123, Strasbourg, 1986).

In vivo experiments involved 10 male Wistar rats (weight: 200-250 g, age: 3 months). Before studies of bioresorption in vivo, СаСО₃ cores were sterilized in autoclave at 110°С for 1 h. Each weighed amount of СаСО₃ (10 mg) intended for an experiment in each of two locations in one animal was carefully hermetically packed in aluminum foil. The animals were operated under general anesthesia (intraperitoneal injections of Zoletil 100 (0.1 mL) and Rometar (20 mg/mL) solutions, 0.0125 mL per 0.1 kg of animal body mass). The samples were placed into thigh great adductor muscles (musculus adductor magnus) of both hind extremities. Then the wounds were sutured layer by layer using atraumatic needles and Prolene 4-0 suture. After outer suturing, the rats were caged individually, were fed standard diet, and had free access to water. All animals were active after surgery; no inflammation in the implantation area was observed, which is indicative of the absence of detrimental effects of implantation.

Histological studies

In 1 and 2 weeks after operation, samples of muscle tissue containing СаСО₃ were fixed with 10% neutral formalin in phosphate buffer (рН=7.4) for not less than 24 hrs, dehydrated using a series of ethanol solutions with increasing concentrations, and enclosed in paraffin blocks according to the standard histological technique. The paraffin cuts (5 μm in width) transverse to muscular fibers were obtained with the use of an Accu-Cut SRT 200 microtome (Sakura, Japan) and stained with Mayer hematoxylin and eosin (Bio-Optica, Italy). The connective tissue was visualized according to the Mallory method (BioVitrum, Russia). Microscopic analysis was performed using a Leica DM750 light microscope (Germany) with a 10× ocular and 4, 10, 40, and 100× objectives. Images were recorded with an ICC50 camera (Leica, Germany).

Results

Influence of human blood plasma on the structure of СаСО₃ cores

Blood plasma contains phosphate ions, which enter into reaction with СаСО₃ vaterites; as a result, macroporous СаНРО₄ structures are gradually formed [14]. It is seen in the SEM images of СаСО₃ vaterites (Fig. 1) that the objects with increasingly loose structure are formed with time; they consist of needle-like subunits less than 1 μm in diameter.

Phosphorus content in the studied structures was determined by energy-dispersive spectroscopy (see Table 1).

The EDS data show that phosphorus content in transformed structures increases with time; this result confirms that ion exchange reaction indeed occurs in СаСО₃ vaterites.

Figure 1. Microphotographs of СаСО₃ vaterites taken upon interaction with human blood plasma for various periods of time: A – 2 hrs; B – 24 hrs; C – 50 hrs

Transformation of СаСО₃ vaterites upon intramuscular administration

After injection of СаСО₃ vaterites into thigh great adductor muscles (musculus adductor magnus) of both hind extremities in rats, needle-like structures were formed (Fig. 2) and then gradually disappeared in two weeks due to bioresorption. Presumably, these needles are aragonites (one of three СаСО₃ polymorphs). Fig. 2B presents the magnified image of the area where vaterites were introduced and then transformed into aragonites (1 week after operation). As was mentioned in Introduction, aragonites (non-porous elongated structures) are one of three morphological modifications of calcium carbonate, along with non-porous (usually cubic) calcites and porous spherical vaterites (which are used as components of target drug delivery systems). Transformation of vaterites during their use in delivery systems into calcites is frequently observed [13]. Formation of aragonite-like structures in the process of bioresorption of СаСО₃ vaterites was revealed in the present work for the first time.

Figure 2. Histological cuts of rat muscle tissue obtained in 1 week after implantation of СаСО₃ vaterites. Staining with hematoxylin and eosin; objectives 10× (а), 40× (b)

Discussion

he reason for transformation of porous СаСО₃ vaterites (diameter: 1 – 3 μm) into needle-like aragonites (length: 30 – 150 μm, width: 10 – 40 μm) in muscle tissue still remains unclear. It may be suggested that morphological transformation of vaterites is influenced by the following factors. First, there is a difference between pH values of muscle tissue and blood or its components (pH of muscle tissue is lower). The second factor involves peculiarities of metabolic processes, mainly, exchange of carbon dioxide. Upon interaction with water, carbon dioxide forms carbonic acid, which reacts with calcium carbonate. Among other factors are intensive action of immune cells, and, finally, mechanic action related to muscle contraction. This issue should be investigated further.

The comparison between our results and the literature data on transformation of СаСО₃ vaterites with encapsulated Fe₃O₄ nanoparticles (which occurred after shallow transdermal injection into rat body [23]) shows that no vaterite modification in muscle tissue was observed. The histological sections prepared in one week after transdermal administration show spherical structures almost similar to the initial cores. In two weeks after operation, vaterites underwent bioresorption, and Fe₃O₄ nanoparticles were released. These data may indirectly confirm our hypothesis concerning the influence of the above factors on transformation of CaCO₃ vaterites in muscle tissue.

Bioresorption of vaterites in blood plasma in vitro is also completed in relatively short period of time (several weeks), while plasma composition remains mostly unchanged.

The main advantage of the DS based on CaCO₃ vaterites intended for intramuscular administration of antitumor preparations is the fact that modified carbonate cores undergo complete bioresorption in 2 weeks in vivo and exert no negative influence on the surrounding tissues. The fact that aragonites are formed in the muscles once again indicates the ambiguity of applying the conclusions obtained from in vitro experiments to the in vivo behavior of the studied objects.

The obtained results confirm ability of porous calcium carbonate cores for bioresorption and their safety for medicinal use, which allows us to recommend porous CaCO₃ vaterites for further experimental studies as components of target drug delivery systems.

Conflict of interests

None declared.

References

1. Volodkin DV, Petrov AI, Prevot M, Sukhorukov GB. Matrix polyelectrolyte microcapsules: new system for macromolecule encapsulation. Langmuir. 2004; 20: 3398-3406.
2. She Z, Wang CX, Li J, Sukhorukov GB, Antipina MN. Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer microcapsules and its controlled release for enhancing cell proliferation. Biomacromolecules. 2012; 13(7): 2174-2180. DOI: 10.1021/bm3005879.
3. Liu D, Jiang G, Yu W, Tong Z, Kong X, Yao J. Oral delivery of insulin using CaCO3-based composite nanocarriers with hyaluronic acid coatings. Materials Letters. 2017; 188: 263-266. DOI: 10.1016/j.matlet.2016.10.117.
4. Ramalapaa B, Crasson O, Vandevenne M, Cordonnier T, Galleni M, Boury F. Protein-polysaccharide complexes for enhanced protein delivery in hyaluronic acid templated calcium carbonate microparticles. J Mater Chem B. 2017; 5: 7360-7368. DOI: 10.1039/C7TB01538K.
5. Peng C, Zhao Q, Gao C. Sustained delivery of doxorubicin by porous CaCO3 and chitosan/alginate multilayers-coated CaCO3 microparticles. Colloids and Surfaces A: Physicochem Eng Aspects. 2010; 353:132–139. DOI:10.1016/j.colsurfa.2009.11.004.
6. Sudareva N, Suvorova O, Saprykina N, Vilesov A, Bel’tyukov P, Petunov S. Alginate-containing systems for oral delivery of superoxide dismutase. Comparison of various configurations and their properties. J Microencapsulation. 2016; 33(5): 487-496. DOI: 10.1080/02652048.2016.1206146.
7. Zhao D, Zhuo R, Cheng S. Alginate modified nanostructured calcium carbonate with enhanced delivery efficiency for gene and drug delivery. Mol BioSystems. 2012; 8: 753-759. DOI: 10.1039/c1mb05337j.
8. Liang P, Liu C, Zhuo R, Cheng S. Self-assembled inorganic/organic hybrid nanoparticles with multi-functionalized surfaces for active targeting drug delivery. J Mat Chem B. 2013; 1: 4243-4250. DOI: 10.1039/C3TB20455C.
9. Trushina DB, Akasov RA, Khovankina AV, Borodina TN, Bukreeva TV, Markvicheva EA. Doxorubicin-loaded biodegradable capsules: Temperature induced shrinking and study of cytotoxicity in vitro. J Mol Liquids. 2019; 284: 15215-224. DOI: 10.1016/j.molliq.2019.03.152.
10. Binevski PV, Balabushevich NG, Uvarova VI, Vikulina AS, Volodkin D. Bio-friendly encapsulation of superoxide dismutase into vaterite CaCO3 crystals. Enzyme activity, release mechanism, and perspectives for ophthalmology. Colloids and Surfaces B: Biointerfaces. 2019; 181: 437-449. DOI: 10.1016/j.colsurfb.2019.05.077.
11. Parakhonskiy B, Tessarolo F, Haase A, Antolini R. Dependence of sub-micron vaterite container release properties on pH and ionic strength of the surrounding solution. Adv Sci Technology. 2013; 86: 81-85. DOI: 10.4028/www.scientific. net/AST.86.81.
12. Ogino T, Suzuki T, Sawada K. The formation and transformation mechanism of calcium carbonate in water. Geochim Cosmochim Acta. 1987; 51(10): 2757-2767.
13. Sergeeva A, Sergeev R, Lengert E, Zakharevich A, Parakhonskiy B, Gorin D, Sergeev S, Volodkin D. Composite magnetite and protein containing CaCO3 crystals. External manipulation and vaterites-calcite recrystallization-mediated release performance. ACS Appl Mater Interfaces. 2015; 7:21315-21325. DOI: 10.1021/acsami. 5b05848.
14. Sudareva NN, Saprykina NN, Popova EV, Vilesov AD. Porous calcium carbonate cores as templates for preparation of peroral proteins delivery systems. The influence of composition of simulated gastrointestinal fluids on the structure and morphology of carbonate cores. Chapter 4. In: "Calcium Carbonate: Occurrence, Characterization and Applications". (Ed. A.Cohen), Nova Science Publishers, Inc (NOVA). 2015, pp.73-95.
15. Sudareva N, Suvorova O, Saprykina N, Smirnova N, Bel'tiukov P, Petunov S, Radilov А, Vilesov A. Two-level delivery systems based on CaCO₃ cores for oral administration of therapeutic peptides. J Microencapsulation. 2018; 35: 619-634. DOI:10.1080/02652048.2018.155924.
16. Sudareva N, Popova H, Saprykina N, Bronnikov S. Structural optimization of calcium carbonate cores as templates for protein encapsulation. J Microencapsulation. 2014; 3(14): 333-343. DOI: 10.3109/02652048.2013.858788.
17. Parakhonskiy BV, Haase A, Antolini R. Sub-micrometer vaterites containers: synthesis, substance loading, and release. Angew Chem Int. Edition. 2012; 51: 1195-1197.
18. Zou Z, Bertinetti L, Politi Y, Fratzl P, Habraken WJ. Control of polymorph selection in amorphous calcium carbonate crystallization by poly(aspartic acid): two different mechanisms. Small. 2017; 13:1603100. DOI: 10.1002/smll.201603100.
19. Nagaraja AT, Pradhan S, McShane MJ. Poly(vinylsulfonic acid) assisted synthesis of aqueous solution stable vaterite calcium carbonate nanoparticles. J Colloid Interface Sci. 2014; 418: 366-372.
20. Zhao D, Zhuo R, Cheng S. Alginate modified nanostructured calcium carbonate with enhanced delivery efficiency for gene and drug delivery. Mol Biosystems. 2012; 8:753-759.
21. Gusliakova O, Atochina-Vasserman EN, Sindeeva O, Sindeev S, Pinyaev S, Pyataev N, Revin V, Sukhorukov GB, Gorin D, Gow AJ. Use of submicron vaterite particles serves as an effective delivery vehicle to the respiratory portion of the lung. Front Pharmacol: Exp Pharmacol and Drug Discovery. 2018; 9: Article 559. DOI: 10.3389/fphar.2018.00559.
22. Borodina, TN, Trushina DB, Marchenko IV, Bukreeva TV. Calcium carbonate-based mucoadhesive microcontainers for intranasal delivery of drugs bypassing the blood-brain barrier. BioNanoScience. 2016; 6: 261-268. DOI: 10.1007/s12668-016-0212-2.
23. Genina EA, Svenskaya YI, Yanina IY, Dolotov LE, Navolokin NA, Bashkatov AN, Terentyuk GS, Bucharskaya AB, Maslyakova GN, Gorin DA, Tuchin VV, Sukhorukov GB. In vivo optical monitoring of transcutaneous delivery of calcium carbonate microcontainers. Biomed Opt Express. 2016; 7: 2082-2087. DOI: 10.1364/BOE.7.002082.
24. Ohgushi H, Okumura M, Yoshikawa T, Inboue K, Senpuku N, Tamai S, Shors EC. Bone formation process in porous calcium carbonate and hydroxyapatite. J Biomed Mater Res. 1992; 26 (7): 885-895. DOI: 10.1002/jbm.820260705.
25. Trushina DB, Bukreeva TV, Kovalchuk MV, Antipina MN. CaCO3 vaterite microparticles for biomedical and personal care applications. Materials Sci Engineering C. 2014; 45: 644-658. DOI: 10.1016/j.msec.2014.04.050.
26. Parakhonskiy B, Zyuzin MV, Yashchenok A, Carregal-Romero S, Rejman J, Möhwald H. The influence of the size and aspect ratio of anisotropic, porous CaCO₃ particles on their uptake by cells. J Nanobiotechnol. 2015; 13: Article 53. doi: 10.1186/s12951-015-0111-7.

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Сударева^1,2, Павел В. Попрядухин^1,2, Наталья Н. Сапрыкина¹, Ольга М. Суворова¹, Галина Ю. Юкина², Олег В. Галибин², Александр Д. Вилесов^1,2</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(338) "

Наталья Н. Сударева^1,2, Павел В. Попрядухин^1,2, Наталья Н. Сапрыкина¹, Ольга М. Суворова¹, Галина Ю. Юкина², Олег В. Галибин², Александр Д. Вилесов^1,2

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¹ Институт высокомолекулярных соединений РАН, Санкт-Петербург, Россия
² Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

" ["TYPE"]=> string(4) "HTML" } ["~DESCRIPTION"]=> string(0) "" ["~NAME"]=> string(22) "Организации" ["~DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } } ["SUMMARY_RU"]=> array(36) { ["ID"]=> string(2) "27" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:01:20" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(29) "Описание/Резюме" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_RU" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "27" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "26448" ["VALUE"]=> array(2) { ["TEXT"]=> string(2847) "<p style="text-align: justify;">Успехи в лечении большинства онкологических заболеваний связаны с применением действенных и в различной мере токсичных противоопухолевых препаратов. Во многих случаях химиотерапия требует максимальной локализации препарата в зоне опухоли. Поэтому наиболее эффективным методом является введение медицинских препаратов (MП) непосредственно в опухоль или применение таргетных систем их доставки. Второй из этих методов дает возможность снизить общую токсичность МП и достичь пролонгированного терапевтического эффекта из-за равномерного, контролируемого по времени выхода МП в опухолевую ткань. В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО₃ (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.</p> <h2>Ключевые слова</h2> <p style="text-align: justify;">Противоопухолевые препараты, системы доставки, СаСО₃, ватериты, плазма крови, внутримышечное введение, биорезорбция.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2767) "

Успехи в лечении большинства онкологических заболеваний связаны с применением действенных и в различной мере токсичных противоопухолевых препаратов. Во многих случаях химиотерапия требует максимальной локализации препарата в зоне опухоли. Поэтому наиболее эффективным методом является введение медицинских препаратов (MП) непосредственно в опухоль или применение таргетных систем их доставки. Второй из этих методов дает возможность снизить общую токсичность МП и достичь пролонгированного терапевтического эффекта из-за равномерного, контролируемого по времени выхода МП в опухолевую ткань. В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО₃ (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.

Ключевые слова

Противоопухолевые препараты, системы доставки, СаСО₃, ватериты, плазма крови, внутримышечное введение, биорезорбция.

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Natalia N. Sudareva^1,2, Pavel V. Popryadukhin^1,2, Natalia N. Saprykina¹, Olga M. Suvorova¹, Galina Yu. Yukina², Oleg V. Galibin², Aleksandr D. Vilesov^1,2

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¹ Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
² Pavlov University, St. Petersburg, Russia

Correspondence
Dr. Natalia N. Sudareva, Research Institute of Macromolecular Compounds, Bolshoi Prosp. 31 (V.O.), 199004, St. Petersburg, Russia
E-mail: nnsas@mail.ru

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Successful treatment of the majority of oncological diseases that affect solid organs is related to appropriate use of potent and (to varying degrees) toxic antitumor drugs. In a number of cases, chemotherapy requires the maximum localized action of a drug in the tumor area. The most efficient methods of drug administration are introducing medicinal compounds (MC) directly into the tumor or use of target drug delivery systems. The second method makes it possible to decrease general toxicity of MC, and to reach prolonged therapeutic action due to uniform and time-controlled release of a MC into tumor tissue.

In the present work, we studied behavior of porous spherical СаСО₃ vaterites (components of delivery systems for antitumor drugs) in various environments (human blood plasma, rat muscle tissue). It was demonstrated that the studied drug carriers undergo morphological transformations and are destructed with time. In blood plasma, due to ion exchange reactions, vaterites are transformed into gradually disintegrating needle-like structures (as shown by scanning electron microscopy and energy dispersive spectroscopy). Similar processes were observed in muscle tissue: in three days, spheres were transformed into needle-like structures and then underwent complete bioresorption.

Keywords

Anticancer drugs delivery systems, СаСО₃ vaterites, blood plasma, intramuscular administration, bioresorption.

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Sudareva^1,2, Pavel V. Popryadukhin^1,2, Natalia N. Saprykina¹, Olga M. Suvorova¹, Galina Yu. Yukina², Oleg V. Galibin², Aleksandr D. Vilesov^1,2</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(237) "

Natalia N. Sudareva^1,2, Pavel V. Popryadukhin^1,2, Natalia N. Saprykina¹, Olga M. Suvorova¹, Galina Yu. Yukina², Oleg V. Galibin², Aleksandr D. Vilesov^1,2

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Natalia N. Sudareva^1,2, Pavel V. Popryadukhin^1,2, Natalia N. Saprykina¹, Olga M. Suvorova¹, Galina Yu. Yukina², Oleg V. Galibin², Aleksandr D. Vilesov^1,2

" } ["SUMMARY_EN"]=> array(37) { ["ID"]=> string(2) "39" ["TIMESTAMP_X"]=> string(19) "2015-09-02 18:02:59" ["IBLOCK_ID"]=> string(1) "2" ["NAME"]=> string(21) "Description / Summary" ["ACTIVE"]=> string(1) "Y" ["SORT"]=> string(3) "500" ["CODE"]=> string(10) "SUMMARY_EN" ["DEFAULT_VALUE"]=> array(2) { ["TEXT"]=> string(0) "" ["TYPE"]=> string(4) "HTML" } ["PROPERTY_TYPE"]=> string(1) "S" ["ROW_COUNT"]=> string(1) "1" ["COL_COUNT"]=> string(2) "30" ["LIST_TYPE"]=> string(1) "L" ["MULTIPLE"]=> string(1) "N" ["XML_ID"]=> string(2) "39" ["FILE_TYPE"]=> string(0) "" ["MULTIPLE_CNT"]=> string(1) "5" ["TMP_ID"]=> NULL ["LINK_IBLOCK_ID"]=> string(1) "0" ["WITH_DESCRIPTION"]=> string(1) "N" ["SEARCHABLE"]=> string(1) "N" ["FILTRABLE"]=> string(1) "N" ["IS_REQUIRED"]=> string(1) "N" ["VERSION"]=> string(1) "1" ["USER_TYPE"]=> string(4) "HTML" ["USER_TYPE_SETTINGS"]=> array(1) { ["height"]=> int(200) } ["HINT"]=> string(0) "" ["PROPERTY_VALUE_ID"]=> string(5) "26454" ["VALUE"]=> array(2) { ["TEXT"]=> string(1668) "<p style="text-align: justify;">Successful treatment of the majority of oncological diseases that affect solid organs is related to appropriate use of potent and (to varying degrees) toxic antitumor drugs. In a number of cases, chemotherapy requires the maximum localized action of a drug in the tumor area. The most efficient methods of drug administration are introducing medicinal compounds (MC) directly into the tumor or use of target drug delivery systems. The second method makes it possible to decrease general toxicity of MC, and to reach prolonged therapeutic action due to uniform and time-controlled release of a MC into tumor tissue.</p> <p style="text-align: justify;">In the present work, we studied behavior of porous spherical СаСО₃ vaterites (components of delivery systems for antitumor drugs) in various environments (human blood plasma, rat muscle tissue). It was demonstrated that the studied drug carriers undergo morphological transformations and are destructed with time. In blood plasma, due to ion exchange reactions, vaterites are transformed into gradually disintegrating needle-like structures (as shown by scanning electron microscopy and energy dispersive spectroscopy). Similar processes were observed in muscle tissue: in three days, spheres were transformed into needle-like structures and then underwent complete bioresorption.</p> <h2>Keywords</h2> <p style="text-align: justify;">Anticancer drugs delivery systems, СаСО₃ vaterites, blood plasma, intramuscular administration, bioresorption.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(1566) "

Successful treatment of the majority of oncological diseases that affect solid organs is related to appropriate use of potent and (to varying degrees) toxic antitumor drugs. In a number of cases, chemotherapy requires the maximum localized action of a drug in the tumor area. The most efficient methods of drug administration are introducing medicinal compounds (MC) directly into the tumor or use of target drug delivery systems. The second method makes it possible to decrease general toxicity of MC, and to reach prolonged therapeutic action due to uniform and time-controlled release of a MC into tumor tissue.

In the present work, we studied behavior of porous spherical СаСО₃ vaterites (components of delivery systems for antitumor drugs) in various environments (human blood plasma, rat muscle tissue). It was demonstrated that the studied drug carriers undergo morphological transformations and are destructed with time. In blood plasma, due to ion exchange reactions, vaterites are transformed into gradually disintegrating needle-like structures (as shown by scanning electron microscopy and energy dispersive spectroscopy). Similar processes were observed in muscle tissue: in three days, spheres were transformed into needle-like structures and then underwent complete bioresorption.

Keywords

Anticancer drugs delivery systems, СаСО₃ vaterites, blood plasma, intramuscular administration, bioresorption.

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Successful treatment of the majority of oncological diseases that affect solid organs is related to appropriate use of potent and (to varying degrees) toxic antitumor drugs. In a number of cases, chemotherapy requires the maximum localized action of a drug in the tumor area. The most efficient methods of drug administration are introducing medicinal compounds (MC) directly into the tumor or use of target drug delivery systems. The second method makes it possible to decrease general toxicity of MC, and to reach prolonged therapeutic action due to uniform and time-controlled release of a MC into tumor tissue.

In the present work, we studied behavior of porous spherical СаСО₃ vaterites (components of delivery systems for antitumor drugs) in various environments (human blood plasma, rat muscle tissue). It was demonstrated that the studied drug carriers undergo morphological transformations and are destructed with time. In blood plasma, due to ion exchange reactions, vaterites are transformed into gradually disintegrating needle-like structures (as shown by scanning electron microscopy and energy dispersive spectroscopy). Similar processes were observed in muscle tissue: in three days, spheres were transformed into needle-like structures and then underwent complete bioresorption.

Keywords

Anticancer drugs delivery systems, СаСО₃ vaterites, blood plasma, intramuscular administration, bioresorption.

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¹ Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
² Pavlov University, St. Petersburg, Russia

Correspondence
Dr. Natalia N. Sudareva, Research Institute of Macromolecular Compounds, Bolshoi Prosp. 31 (V.O.), 199004, St. Petersburg, Russia
E-mail: nnsas@mail.ru

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¹ Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
² Pavlov University, St. Petersburg, Russia

Correspondence
Dr. Natalia N. Sudareva, Research Institute of Macromolecular Compounds, Bolshoi Prosp. 31 (V.O.), 199004, St. Petersburg, Russia
E-mail: nnsas@mail.ru

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Во многих случаях химиотерапия требует максимальной локализации препарата в зоне опухоли. Поэтому наиболее эффективным методом является введение медицинских препаратов (MП) непосредственно в опухоль или применение таргетных систем их доставки. Второй из этих методов дает возможность снизить общую токсичность МП и достичь пролонгированного терапевтического эффекта из-за равномерного, контролируемого по времени выхода МП в опухолевую ткань. В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО₃ (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.</p> <h2>Ключевые слова</h2> <p style="text-align: justify;">Противоопухолевые препараты, системы доставки, СаСО₃, ватериты, плазма крови, внутримышечное введение, биорезорбция.</p>" ["TYPE"]=> string(4) "HTML" } ["DESCRIPTION"]=> string(0) "" ["VALUE_ENUM"]=> NULL ["VALUE_XML_ID"]=> NULL ["VALUE_SORT"]=> NULL ["~VALUE"]=> array(2) { ["TEXT"]=> string(2767) "

Успехи в лечении большинства онкологических заболеваний связаны с применением действенных и в различной мере токсичных противоопухолевых препаратов. Во многих случаях химиотерапия требует максимальной локализации препарата в зоне опухоли. Поэтому наиболее эффективным методом является введение медицинских препаратов (MП) непосредственно в опухоль или применение таргетных систем их доставки. Второй из этих методов дает возможность снизить общую токсичность МП и достичь пролонгированного терапевтического эффекта из-за равномерного, контролируемого по времени выхода МП в опухолевую ткань. В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО₃ (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.

Ключевые слова

Противоопухолевые препараты, системы доставки, СаСО₃, ватериты, плазма крови, внутримышечное введение, биорезорбция.

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Успехи в лечении большинства онкологических заболеваний связаны с применением действенных и в различной мере токсичных противоопухолевых препаратов. Во многих случаях химиотерапия требует максимальной локализации препарата в зоне опухоли. Поэтому наиболее эффективным методом является введение медицинских препаратов (MП) непосредственно в опухоль или применение таргетных систем их доставки. Второй из этих методов дает возможность снизить общую токсичность МП и достичь пролонгированного терапевтического эффекта из-за равномерного, контролируемого по времени выхода МП в опухолевую ткань. В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО₃ (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.

Ключевые слова

Противоопухолевые препараты, системы доставки, СаСО₃, ватериты, плазма крови, внутримышечное введение, биорезорбция.

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¹ Институт высокомолекулярных соединений РАН, Санкт-Петербург, Россия
² Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

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¹ Институт высокомолекулярных соединений РАН, Санкт-Петербург, Россия
² Первый Санкт-Петербургский государственный медицинский университет им. акад. И. П. Павлова, Санкт-Петербург, Россия

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                    [TEXT] => <p style="text-align: justify;">Достигнут значительный прогресс в иммунотерапии различных злокачественных заболеваний. В области гематологии эти успехи ограничены в основном лимфоидными неоплазиями. Эффективные методы терапии включают моноклональные антитела и Т-клетки с химерным антигенным рецептором (CAR-T-клетки) к антигенам клеток лимфоидного ряда, таким, как CD19, CD20 и антигенам созревания В-клеток (BCMA). Гемтузумаб озогамицин (Миелотарг®) является единственным препаратом, одобренным FDA для иммунотерапии острого миелобластного лейкоза (ОМЛ). Сообщают о нескольких клинических исследованиях антител к CD38 и CD123 с невысокой эффективностью и проблемами безопасности применения. Причинами являются: высокий уровень продукции миелоидных клеток и существенные повреждения нормальных кроветворных клеток в связи с недостаточной специфичностью в отношении клеток ОМЛ. Потенциальными мишенями для анти-ОМЛ терапии являются: (1) антигены системы HLA; (2) минорные антигены гистосовместимости; (3) лейкоз-ассоциированные антигены и (4) лейкоз-специфические антигены.</p>
<p style="text-align: justify;">Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ. </p>
<h2>Ключевые слова</h2>
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Данные в пользу эффективного аллогенного анти-ОМЛ эффекта основаны на исследованиях реципиентов гемопоэтических клеток с реакцией «трансплантат против хозяина» и реципиентов инфузий донорских лимфоцитов. Особой проблемой является относительный дефицит неоантигенов ОМЛ, по сравнению с солидными новообразованиями, что связано с низкой частотой накопленных мутаций. Исследования по клеточной иммунной терапии продолжаются, включая CAR-T-клетки, CAR-NK-клетки и аллогенные NK-клетки. Развиваются подходы с применением синтетической биологии. В настоящее время, кроме гемтузумаба озогамицина, отсутствуют убедительные данные об эффективности иммунной терапии при ОМЛ. 
Ключевые слова
Острый миелобластный лейкоз, мутации, неоантигены, иммунотерапия.
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<br>
<p><b>Correspondence</b><br>
Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, Visiting Professor Haematology, Centre for Haematology Research, Department of Immunology and Inflammation Imperial College London, London, UK<br>
E-mail: robertpetergale@gmail.com</p>


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Imperial College London, London, UK


Correspondence

Robert Peter Gale MD, PhD, DSc(hc), FACP, FRCP, Visiting Professor Haematology, Centre for Haematology Research, Department of Immunology and Inflammation Imperial College London, London, UK

E-mail: robertpetergale@gmail.com


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                    [TEXT] => <p style="text-align: justify;">There is considerable progress in immune therapy of diverse cancers. In haematology these advances are mostly limited to lymphoid cancers. Effective therapies include monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells to lymphoid lineage-antigens such as CD19, CD20 and B-cell maturation antigen (BCMA).  Gemtuzumab ozogamicin (Myelotarg®) is the only FDA-approved immune-based therapy for acute myeloid leukemia (AML). Several clinical trials of antibodies to CD38 and CD123 are reported with unimpressive efficacy and safety concerns. Reasons are higher daily production rates of myeloid cells and unacceptable collateral damage to normal haematopoietic cells because of imperfect specificity for AML cells. Potential targets of anti-AML immune therapy are (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens. Data supporting an effective allogeneic anti-AML effect come from studies in recipients of haematopoietic cell transplants with graft-versus-host disease (GvHD) and recipients of donor lymphocyte infusions (DLI). A special problem is a relative paucity of neo-antigens in AML compared with solid cancers because of a low cumulative mutation frequency. Cell immune therapy trials are in progress including CAR-T-cells, CAR-NK-cells and allogeneic NK-cells. Approaches using synthetic biology are being developed. Presently, except for gemtuzumab ozogamicin there are no convincing data of efficacy of immune therapy in AML.</p>
<h2>Keywords</h2>
<p style="text-align: justify;">Acute myeloid leukemia, mutations, neoantigens, immune therapy.</p>
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There is considerable progress in immune therapy of diverse cancers. In haematology these advances are mostly limited to lymphoid cancers. Effective therapies include monoclonal antibodies and chimeric antigen receptor (CAR)-T-cells to lymphoid lineage-antigens such as CD19, CD20 and B-cell maturation antigen (BCMA).  Gemtuzumab ozogamicin (Myelotarg®) is the only FDA-approved immune-based therapy for acute myeloid leukemia (AML). Several clinical trials of antibodies to CD38 and CD123 are reported with unimpressive efficacy and safety concerns. Reasons are higher daily production rates of myeloid cells and unacceptable collateral damage to normal haematopoietic cells because of imperfect specificity for AML cells. Potential targets of anti-AML immune therapy are (1) HLA antigens; (2) minor histocompatibility antigens; (3) leukemia-associated antigens; and (4) leukemia-specific antigens. Data supporting an effective allogeneic anti-AML effect come from studies in recipients of haematopoietic cell transplants with graft-versus-host disease (GvHD) and recipients of donor lymphocyte infusions (DLI). A special problem is a relative paucity of neo-antigens in AML compared with solid cancers because of a low cumulative mutation frequency. Cell immune therapy trials are in progress including CAR-T-cells, CAR-NK-cells and allogeneic NK-cells. Approaches using synthetic biology are being developed. Presently, except for gemtuzumab ozogamicin there are no convincing data of efficacy of immune therapy in AML.
Keywords
Acute myeloid leukemia, mutations, neoantigens, immune therapy.
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В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО<sub>3</sub> (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.</p>
<h2>Ключевые слова</h2>
<p style="text-align: justify;">Противоопухолевые препараты, системы доставки, СаСО<sub>3</sub>, ватериты, плазма крови, внутримышечное введение, биорезорбция.</p>
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В данной работе мы исследовали поведение пористых сферических частиц ватерита СаСО3 (компонентов системы доставки противоопухолевых препаратов) в различных средах (плазма крови человека, мышечная ткань крыс). Было показано, что исследуемый носитель МП подвергается морфологической трансформации и со временем разрушается. В плазме крови, благодаря ионному обмену, ватериты превращаются в постепенно распадающиеся иглоподобные структуры, что показано с помощью сканирующей электронной микроскопии и энергорассеивающей спектроскопии. Сходные процессы наблюдались в мышечной ткани: в течение 3 дней сферические частицы превращались в иглоподобные структуры и затем подвергались полной биологической резорбции.
Ключевые слова
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                    [TEXT] => <p><sup>1</sup> Institute of Macromolecular Compounds RAS, St. Petersburg, Russia<br>
<sup>2</sup> Pavlov University, St. Petersburg, Russia</p><br>
<p><b>Correspondence</b><br>
Dr. Natalia N. Sudareva, Research Institute of Macromolecular Compounds, Bolshoi Prosp. 31 (V.O.), 199004, St. Petersburg, Russia<br>
E-mail: nnsas@mail.ru</p>
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1 Institute of Macromolecular Compounds RAS, St. Petersburg, Russia

2 Pavlov University, St. Petersburg, Russia


Correspondence

Dr. Natalia N. Sudareva, Research Institute of Macromolecular Compounds, Bolshoi Prosp. 31 (V.O.), 199004, St. Petersburg, Russia

E-mail: nnsas@mail.ru
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                    [TEXT] => <p style="text-align: justify;">Successful treatment of the majority of oncological diseases that affect solid organs is related to appropriate use of potent and (to varying degrees) toxic antitumor drugs. In a number of cases, chemotherapy requires the maximum localized action of a drug in the tumor area. The most efficient methods of drug administration are introducing medicinal compounds (MC) directly into the tumor or use of target drug delivery systems. The second method makes it possible to decrease general toxicity of MC, and to reach prolonged therapeutic action due to uniform and time-controlled release of a MC into tumor tissue.</p>
<p style="text-align: justify;">In the present work, we studied behavior of porous spherical СаСО<sub>3</sub> vaterites (components of delivery systems for antitumor drugs) in various environments (human blood plasma, rat muscle tissue). It was demonstrated that the studied drug carriers undergo morphological transformations and are destructed with time.
In blood plasma, due to ion exchange reactions, vaterites are transformed into gradually disintegrating needle-like structures (as shown by scanning electron microscopy and energy dispersive spectroscopy). Similar processes were observed in muscle tissue: in three days, spheres were transformed into needle-like structures and then underwent complete bioresorption.</p>
<h2>Keywords</h2>
<p style="text-align: justify;">Anticancer drugs delivery systems, СаСО<sub>3</sub> vaterites, blood plasma, intramuscular administration, bioresorption.</p>
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Successful treatment of the majority of oncological diseases that affect solid organs is related to appropriate use of potent and (to varying degrees) toxic antitumor drugs. In a number of cases, chemotherapy requires the maximum localized action of a drug in the tumor area. The most efficient methods of drug administration are introducing medicinal compounds (MC) directly into the tumor or use of target drug delivery systems. The second method makes it possible to decrease general toxicity of MC, and to reach prolonged therapeutic action due to uniform and time-controlled release of a MC into tumor tissue.
In the present work, we studied behavior of porous spherical СаСО3 vaterites (components of delivery systems for antitumor drugs) in various environments (human blood plasma, rat muscle tissue). It was demonstrated that the studied drug carriers undergo morphological transformations and are destructed with time.
In blood plasma, due to ion exchange reactions, vaterites are transformed into gradually disintegrating needle-like structures (as shown by scanning electron microscopy and energy dispersive spectroscopy). Similar processes were observed in muscle tissue: in three days, spheres were transformed into needle-like structures and then underwent complete bioresorption.
Keywords
Anticancer drugs delivery systems, СаСО3 vaterites, blood plasma, intramuscular administration, bioresorption.
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