Preview

Ateroscleroz

Advanced search

Apolipoprotein А-I as a transport form of cytostatics in Ehrlich ascitic carcinoma cells

https://doi.org/10.52727/2078-256X-2024-20-4-355-361

Abstract

One of the pressing issues of modern pharmacology remains the development of drugs with targeted antitumor action, or the creation of dosage forms of selective action of already known cytostatics in order to increase the effectiveness of chemotherapy and reduce the overall toxic effect on the body. In this work, it is proposed to use apolipoprotein A-I as a transport form of the antitumor drugs actinomycin D, doxorubicin, vinblastine and melphalan. Material and methods. Apolipoprotein A-I was isolated from the high-density lipoprotein fraction of human blood plasma. Apolipoprotein A-I was labeled with 1 % fluoresceinisothiocyanate (FITC). For the experiments, we used male C57Bl mice weighing 20–25 g. Ehrlich ascites carcinoma cells were obtained from peritoneal exudate 9–10 days after transplantation. Fluorescent analysis was carried out on an AxioImager Z1 “Zeiss” microscope using an AxioCamMRc digital camera and AxioVision V.4.5 software. The absorption spectra of antitumor drugs in the optical region of electromagnetic radiation were studied using an Evolution 300 spectrophotometer (Thermo Fisher Scientific, USA). Results. The paper presents the results indicating the ability of FITC-labeled apolipoprotein A-I to enter tumor cells. Using the method of column chromatography and spectrofluorimetry, the formation of apolipoprotein A-Icytostatic complex (actinomycin D, doxorubicin, melphalan, vinblastine) was shown. Analysis of the content of drugs in tumor cell lysates showed that absorption (internalization) was more pronounced during incubation of cells with cytostatics in complex forms with apolipoprotein A-I compared with the absorption of cytostatics by cells without a carrier. Conclusions. It has been established that apolipoprotein A-I can be a direct carrier of cytostatics into the cells of Ehrlich ascites carcinoma.

About the Authors

N. V. Trifonova
Research Institute of Biochemistry of Federal Research Center for Fundamental and Translational Medicine
Russian Federation

Nataliya V. Trifonova, researcher of laboratory of medical biotechnology,

2, Timakov st., Novosibirsk, 630117.



R. A. Knyazev
Research Institute of Biochemistry of Federal Research Center for Fundamental and Translational Medicine
Russian Federation

Roman A. Knyazev, candidate of biological sciences, senior researcher of laboratory of medical biotechnology,

2, Timakov st., Novosibirsk, 630117.



M. V. Kotova
Research Institute of Biochemistry of Federal Research Center for Fundamental and Translational Medicine
Russian Federation

Mariya V. Kotova, researcher of laboratory of medical biotechnology,

2, Timakov st., Novosibirsk, 630117.



L. M. Polyakov
Research Institute of Biochemistry of Federal Research Center for Fundamental and Translational Medicine
Russian Federation

Lev M. Polyakov, doctor of medical sciences, professor, head of the laboratory of medical biotechnology,

2, Timakov st., Novosibirsk, 630117.



References

1. Xia W., Tao Z., Zhu B., Zhang W., Liu C., Chen S., Song M. Targeted delivery of drugs and genes using polymer nanocarriers for cancer therapy. Int. J. Mol. Sci., 2021; 22 (17): 9118. doi: 10.3390/ijms22179118

2. Kenchegowda M., Rahamathulla M., Hani U., Begum M.Y., Guruswamy S., Osmani R.A.M., Gowrav M.P., Alshehri S., Ghoneim M.M., Alshlowi A., Gowda D.V. Smart nanocarriers as an emerging platform for cancer therapy: a review. Molecules, 2021; 27 (1): 146. doi: 10.3390/molecules27010146

3. Peer D., Karp J.M., Hong S., Farokhzad O.C., Margalit R., Langer R. Nanocarriers as an emerging platform for cancer therapy. In: Nano-enabled medical applications. Eds. L.P. Balogh. New York: Jenny Stanford Publishing, 2020. P. 61–91.

4. Князев Р.А., Трифонова Н.В., Поляков Л.М. Транспортная форма противоопухолевых препаратов доксорубицина и мелфалана на основе аполипопротеина А-I плазмы крови. Современные проблемы науки и образования, 2016; 6: 221. [Knyazev R.A., Trifonova N.V., Polyakov L.M. ApolipoproteinA-I as carrier anticancer drugs doxorubicin and melphalan. Modern Problems of Science and Education, 2016; 6: 221. (In Russ.)].

5. Панин Л.Е., Поляков Л.М., Усынин И.Ф., Суменкова Д.В., Князев Р.А. Влияние кортикостероидов в комплексе с аполипопротеином А-1 на биосинтез белка в культуре гепатоцитов. Проблемы эндокринологии, 2009; 55 (3): 45–47. doi:10.14341/probl200955345-47 [Panin L.E., Polyakov L.M., Usynin I.F., Sumenkova D.V., Knyazev R.A. Effect of a complex of corticosteroids with apolipoprotein A-I on protein biosynthesis in cultured hepatocytes. Problems of Endocrinology, 2009; 55(3):45–47. (In Russ.)]. doi: 10.14341/probl200955345-47

6. Chapman M.J., Goldstein S., Lagrange D., Laplaud P.M. A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum. Journal of Lipid Research, 1981; 22(2): 339–358. doi: 10.1016/с0022-2275(20)35376-1

7. Nguyen T.T., Nguyen H.N., Nghiem T.H.L., Do X.H., To T.T., Do T.X.P., Do D.L., Nguyen H.G., Nguyen H.M., Nguyen N.D., Luu M.Q., Nguyen T.N., Nguyen T.B.N., Nguyen V.T., Pham V.T., Than U.T.T., Hoang T.M.N. High biocompatible FITC-conjugated silica nanoparticles for cell labeling in both in vitro and in vivo models. Sci. Rep., 2024; 14 (1): 6969. doi: 10.1038/с41598-024-55600-w

8. Востроилова Г.А., Хохлова Н.А., Шабанов Д.И., Михайлов Е.В., Корчагина А.А., Шабунин Б.В., Некрасов А.В. Характеристика модели асцитной карциномы Эрлиха и перспективы ее применения в экспериментальной фармакологии ветеринарных препаратов. Лабораторные животные для научных исследований, 2023; 3: 108–117. doi: 10.57034/2618723x-2023-03-10 [Vostroilova G.A., Hohlova N.A., Shabanov D.I., Mikhaylov E.V., Korchagina A.A., Shabunin B.V., Nekrasov A.V. Characteristics of the Ehrlich ascites carcinoma model and prospects for its application in experimental pharmacology of veterinary drugs. Laboratory Animals for Science, 2023; 3: 108–117. (In Russ.)]. doi: 10.57034/2618723x-2023-03-10

9. Князев Р.А., Трифонова Н.В., Поляков Л.М. Изучение способности липопротеинов высокой плотности и аполипопротеина А-I связывать и транспортировать противоопухолевые препараты в клетки асцитной карциномы Эрлиха. Междунар. журн. прикл. и фундамент. исследований, 2015; 11: 538–542. [Knyazev R.A., Trifonova N.V., Polyakov L.M. Study of the ability of high density lipoprotein and apolipoprotein A-I and transport of anticancer drugs in Ehrlich ascites carcinoma cell. International Journal of Applied and Basic Research, 2015; 11: 538– 542. (In Russ.)].

10. Князев Р.А., Трифонова Н.В., Поляков Л.М. Изучение эффективности цитостатического действия комплекса аполипопротеина A-I с винбластином. Современные проблемы науки и образования, 2015; 6: 649. [Knyazev R.A., Trifonova N.V., Polyakov L.M. Study cytostatic effect of complex apolipoprotein A-I with vinblastine. Modern Problems of Science and Education, 2015; 6: 649. (In Russ.)].

11. Alavi M., Hamidi M. Passive and active targeting in cancer therapy by liposomes and lipid nanoparticles. Drug. Metab. Pers. Ther., 2019: 34 (1): 20180032. doi: 10.1515/dmpt-2018-0032

12. Daraee H., Etemadi A., Kouhi M., Alimirzalu S., Akbarzadeh A. Application of liposomes in medicine and drug delivery. Artif. Cells Nanomed. Biotechnol., 2016; 44(1), 381–391. doi: 10.3109/21691401.2014.953633

13. Nikolova M.P., Kumar E.M., Chavali M.S. Updates on responsive drug delivery based on liposome vehicles for cancer treatment. Pharmaceutics, 2022; 14 (10): 2195. doi: 10.3390/pharmaceutics14102195

14. Olusanya T.O., Haj Ahmad R.R., Ibegbu D.M., Smith J.R., Elkordy A.A. Liposomal drug delivery systems and anticancer drugs. Molecules, 2018; 23 (4): 907. doi: 10.3390/molecules23040907

15. Xu B., Gillard B.K., Gotto Jr. A.M., Rosales C., Pownall H.J. ABCA1-derived nascent high-density lipoprotein–apolipoprotein AI and lipids metabolically segregate. Arterioscler. Thromb. Vasc. Biol., 2017; 37 (12): 2260–2270. doi: 10.1161/ATVBAHA.117.310290


Review

For citations:


Trifonova N.V., Knyazev R.A., Kotova M.V., Polyakov L.M. Apolipoprotein А-I as a transport form of cytostatics in Ehrlich ascitic carcinoma cells. Ateroscleroz. 2024;20(4):355-361. (In Russ.) https://doi.org/10.52727/2078-256X-2024-20-4-355-361

Views: 68


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2078-256X (Print)
ISSN 2949-3633 (Online)