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  4. T. 40, № 4, 2023

Биологические мембраны: Журнал мембранной и клеточной биологии, 2023, T. 40, № 4, стр. 259-272

Мембраноактивные митохондриально направленные агенты и системы доставки препаратов противоопухолевого действия

А. П. Садиков a, З. Г. Дениева b, У. А. Буданова a, *, Ю. Л. Себякин a

a МИРЭА – Российский технологический университет (Институт тонких химических технологий им. М.В. Ломоносова)
119571 Москва, Россия

b Институт физической химии и электрохимии им. А.Н. Фрумкина РАН
119071 Москва, Россия

* E-mail: c-221@yandex.ru

Поступила в редакцию 28.02.2023
После доработки 30.03.2023
Принята к публикации 03.04.2023

Аннотация

Митохондрии являются “энергетическими станциями”, без которых невозможно нормальное функционирование живой клетки. Благодаря разнообразию процессов, которые протекают при участии митохондрий, а также особенностям митохондрий здоровых и опухолевых клеток, эта органелла представляет собой привлекательную мишень для терапии онкологических заболеваний. В данном обзоре рассмотрены разнообразные подходы к созданию диагностических и терапевтических средств, селективно направленных на митохондрии пораженных клеток. Описаны основные митохондриально направленные лиганды, их конъюгация с известными противоопухолевыми препаратами, а также комбинации с распространенными средствами доставки лекарственных агентов, применяемых в целях медицины.

Ключевые слова: митохондрии, наночастицы, делокализованные катионы, противоопухолевые средства

Список литературы

  1. Reichert A.S., Neupert W. 2004. Mitochondriomics or what makes us breathe. Trends in genetics. 20 (11), 555–562. https://doi.org/10.1016/j.tig.2004.08.012

  2. Cho H., Cho Y.Y., Shim M.S., Lee J.Y., Lee H.S., Kang H.C. 2020. Mitochondria-targeted drug delivery in cancers. Biochim. Biophys. Acta Mol. Basis Dis. 1866 (8), 165808. https://doi.org/10.1016/j.bbadis.2020.165808

  3. Buchke S., Sharma M., Bora A., Relekar M., Bhanu P., Kumar J. 2022. Mitochondria-targeted, nanoparticle-based drug-delivery systems: Therapeutics for mitochondrial disorders. Life (Basel). 12 (5), 657. https://doi.org/10.3390/life12050657

  4. Nelson D.L., Cox M.M. 2021. Lehninger Principles of Biochemistry. Bloomsbury Academic. 1260 p.

  5. Рем К.-Г., Кельман Я. 2021. Наглядная биохимия. М.: Бином, Лаборатория знаний. 512 с.

  6. Bleck C.K.E., Kim, Y., Willingham, T.B., Glancy, B. 2018. Subcellular connectomic analyses of energy networks in striated muscle. Nat. Commun. 9, 5111.

  7. Valente A.J., Fonseca J., Moradi F., Foran G., Necakov A., Stuart J.A. 2019. Quantification of mitochondrial network characteristics in health and disease. Adv. Exp. Med. Biol. 1158, 183–196. https://doi.org/10.1007/978-981-13-8367-0_10

  8. Белякович А.Г. 1990. Изучение митохондрий и бактерий с помощью соли тетразолия п-НТФ. ОНТИ НЦБИ АН СССР. 232 с.

  9. Tait S.W., Green D.R. 2013. Mitochondrial regulation of cell death. Cold Spring Harb Perspect Biol. 5 (9), a008706. https://doi.org/10.1101/cshperspect.a008706

  10. S Allemailem K., Almatroudi A., Alsahli M.A., Aljaghwani A., M. El-Kady A., Rahmani A.H., Khan A.A. 2021. Novel strategies for disrupting cancer-cell functions with mitochondria-targeted antitumor drug-loaded nanoformulations. Int. J. Nanomedicine. 16, 3907–3936. https://doi.org/10.2147/IJN.S303832

  11. Dong L., Neuzil J. 2019. Targeting mitochondria as an anticancer strategy. Cancer Commun. (Lond). 39 (1), 1–3. https://doi.org/10.1186/s40880-019-0412-6

  12. Reddy M.S., Bhattacharjee D., Jain N. 2022. Plk1 regulates mutant IDH1 enzyme activity and mutant IDH2 ubiquitination in mitosis. Cell. Signalling. 92, 110279. https://doi.org/10.1016/j.cellsig.2022.110279

  13. Hanaford A.R., Alt J., Rais R., Wang S.Z., Kaur H., Thorek D.L.J., Eberhart C.G., Slusher B.S., Martin A.M., Raabe E.H. 2019. Orally bioavailable glutamine antagonist prodrug JHU-083 penetrates mouse brain and suppresses the growth of MYC-driven medulloblastoma. Transl. Oncol. 12 (10), 1314–1322. https://doi.org/10.1016/j.tranon.2019.05.013

  14. Li Q., Zhong X., Yao W., Yu J., Wang C., Li Z., Lai S., Qu F., Fu X., Huang X., Zhang D., Liu Y., Li H. 2022. Inhibitor of glutamine metabolism V9302 promotes ROS-induced autophagic degradation of B7H3 to enhance antitumor immunity. J. Biol. Chem. 298 (4), 101753. https://doi.org/10.1016/j.jbc.2022.101753

  15. Cao K., Riley J.S., Heilig R., Montes-Gómez A.E., Vringer E., Berthenet K., Cloix C., Elmasry Y., Spiller D.G., Ichim G., Campbell K.J., Gilmore A.P., Tait S.W.G. 2022. Mitochondrial dynamics regulate genome stability via control of caspase-dependent DNA damage. Dev. Cell. 57 (10), 1211–1225. https://doi.org/10.1016/j.devcel.2022.03.019

  16. Forrest M.D. 2015. Why cancer cells have a more hyperpolarised mitochondrial membrane potential and emergent prospects for therapy. BioRxiv. 025197. https://doi.org/10.1101/025197

  17. Weiner-Gorzel K., Murphy M. 2021. Mitochondrial dynamics, a new therapeutic target for triple negative breast cancer. Biochim. Biophys. Acta (BBA) Reviews on Cancer. 1875 (2), 188518. https://doi.org/10.1016/j.bbcan.2021.188518

  18. Bae Y., Jung M.K., Song S.J., Green E.S., Lee S., Park H.S., Jeong S.H., Han J., Mun J.Y., Ko K.S., Choi J.S. 2017. Functional nanosome for enhanced mitochondria-targeted gene delivery and expression. Mitochondrion. 37, 27–40. https://doi.org/10.1016/j.mito.2017.06.005

  19. Zielonka J., Joseph J., Sikora A., Hardy M., Ouari O., Vasquez-Vivar J., Cheng G., Lopez M., Kalyanaraman B. 2017. Mitochondria-targeted triphenylphosphonium-based compounds: syntheses, mechanisms of action, and therapeutic and diagnostic applications. Chem. Rev. 117 (15), 10 043–10 120. https://doi.org/10.1021/acs.chemrev.7b00042

  20. Murphy M.P. 1997. Selective targeting of bioactive compounds to mitochondria. Trends Biotech. 15 (8), 326–330. https://doi.org/10.1016/S0167-7799(97)01068-8

  21. Burns R.J., Smith R.A.J., Murphy M.P. 1995. Synthesis and characterization of thiobutyltriphenylphosphonium bromide, a novel thiol reagent targeted to the mitochondrial matrix. Arch. Biochem. Biophys. 322 (1), 60–68. https://doi.org/10.1006/abbi.1995.1436

  22. Burns R.J., Murphy M.P. 1997. Labeling of mitochondrial proteins in living cells by the thiol probe thiobutyltriphenylphosphonium bromide. Arch. Biochem. Biophys. 339 (1), 33–39. https://doi.org/10.1006/abbi.1996.9861

  23. Smith R.A., Porteous C.M., Gane A.M., Murphy M.P. 2003. Delivery of bioactive molecules to mitochondria in vivo. Proc. Nat. Acad. Sci. USA. 100 (9), 5407–5412. https://doi.org/10.1073/pnas.0931245100

  24. Su Y., Tu Y., Lin H., Wang M.M., Zhang G.D., Yang J., Liu H.K., Su Z. 2022. Mitochondria-targeted Pt (IV) prodrugs conjugated with an aggregation-induced emission luminogen against breast cancer cells by dual modulation of apoptosis and autophagy inhibition. J. Inorg. Biochem. 226, 111653. https://doi.org/10.1016/j.jinorgbio.2021.111653

  25. Huang M., Myers C.R., Wang Y., You M. 2021. Mitochondria as a novel target for cancer chemoprevention: Emergence of mitochondrial-targeting agents. Cancer Prev, Res. 14 (3), 285–306. https://doi.org/10.1158/1940-6207.CAPR-20-0425

  26. Bailly C. 2021. Medicinal applications and molecular targets of dequalinium chloride. Biochem. Pharmacol. 186, 114467. https://doi.org/10.1016/j.bcp.2021.114467

  27. Shi M., Zhang J., Li X., Pan S., Li J., Yang C., Hu H., Qiao M., Chen D., Zhao X. 2018. Mitochondria-targeted delivery of doxorubicin to enhance antitumor activity with HER-2 peptide-mediated multifunctional pH-sensitive DQAsomes. Int. J. Nanomedicine. 13, 4209–4226. https://doi.org/10.2147/IJN.S163858

  28. Bailly C. 2021. Medicinal applications and molecular targets of dequalinium chloride. Biochem. Pharmacol. 186, 114467. https://doi.org/10.1016/j.bcp.2021.114467

  29. Mallick S., Thuy L.T., Lee S., Park J.I., Choi J.S. 2018. Liposomes containing cholesterol and mitochondria-penetrating peptide (MPP) for targeted delivery of antimycin A to A549 cells. Colloids Surf. B. Biointerfaces. 161, 356–364. https://doi.org/10.1016/j.colsurfb.2017.10.052

  30. Somsri S., Mungthin M., Klubthawee N., Adisakwattana P., Hanpithakpong W., Aunpad R.A. 2021. Mitochondria-penetrating peptide exerts potent anti-plasmodium activity and localizes at parasites’ mitochondria. Antibiotics (Basel). 10 (12), 1560. https://doi.org/10.3390/antibiotics10121560

  31. Szeto H.H. 2006. Cell-permeable, mitochondrial-targeted, peptide antioxidants. The AAPS J. 8 (2), E277–E283. https://doi.org/10.1007/BF02854898

  32. Szeto H.H., Schiller P.W. 2011. Novel therapies targeting inner mitochondrial membrane–from discovery to clinical development. Pharm Res. 28 (11), 2669–2679. https://doi.org/10.1007/s11095-011-0476-8

  33. Haftcheshmeh S.M., Jaafari M.R, Mashreghi M., Mehrabian A., Alavizadeh S.H, Zamani P., Zarqi J., Darvishi M.H., Gheybi F. 2021. Liposomal doxorubicin targeting mitochondria: A novel formulation to enhance anti-tumor effects of Doxil® in vitro and in vivo. J. Drug Delivery Sci.Technol. 62, 102351. https://doi.org/10.1016/j.jddst.2021.102351

  34. Bae Y., Kim G., Jessa F., Ko K.S., Han J. 2022. Gallic acid-mitochondria targeting sequence-H3R9 induces mitochondria-targeted cytoprotection. Korean J. Physiol. Pharmacol. 26, 15–24. https://doi.org/10.4196/kjpp.2022.26.1.15

  35. Tee T.T., Cheah Y.H., Hawariah L.P. 2007. F16, a fraction from Eurycoma longifolia jack extract, induces apoptosis via a caspase-9-independent manner in MCF-7 cells. Anticancer Res. 27 (5A), 3425–3430.

  36. Dubinin M.V., Semenova A.A., Nedopekina D.A., Davletshin E.V., Spivak A.Y., Belosludtsev K.N. 2021. Effect of F16-betulin conjugate on mitochondrial membranes and its role in cell death initiation. Membranes. 11 (5), 352. https://doi.org/10.3390/membranes11050352

  37. Dubinin M.V., Semenova A.A., Ilzorkina A.I., Penkov N.V., Nedopekina D.A., Sharapov V.A., Khoroshavina E.I., Davletshin E.V., Belosludtseva N.V., Spivak A.Y., Belosludtsev K.N. 2021. Mitochondria-targeted prooxidant effects of betulinic acid conjugated with delocalized lipophilic cation F16. Free Radic. Biol. Med. 168, 55–69. https://doi.org/10.1016/j.freeradbiomed.2021.03.036

  38. Watley R.L., Awuah S.G., Bio M., Cantu R., Gobeze H.B., Nesterov V.N., Das S.K., D’Souza F., You Y. 2015. Dual functioning thieno-pyrrole fused BODIPY dyes for NIR optical imaging and photodynamic therapy: Singlet oxygen generation without heavy halogen atom assistance. Chem. Asian J. 10, 1335–1343. https://doi.org/10.1002/asia.201500140

  39. Belosludtsev K.N., Ilzorkina A.I., Belosludtseva N.V., Sharapov V.A., Penkov N.V., Serov D.A., Karagyaur M.N., Nedopekina D.A., Davletshin E.V., Solovieva M.E., Spivak A.Y., Kuzmina U.S., Vakhitova Y.V., Akatov V.S., Dubinin M.V. 2022. Comparative study of cytotoxic and membranotropic properties of betulinic acid-F16 conjugate on breast adenocarcinoma cells (MCF-7) and primary human fibroblasts. Biomedicines. 10 (11), 2903. https://doi.org/10.3390/biomedicines10112903

  40. Zhang D., Wen L., Huang R., Wang H., Hu X., Xing D. 2018. Mitochondrial specific photodynamic therapy by rare-earth nanoparticles mediated near-infrared graphene quantum dots. Biomaterials. 153, 14–26. https://doi.org/10.1016/j.biomaterials.2017.10.034

  41. Khailova L.S,. Silachev D.N., Rokitskaya T.I., Avetisyan A.V., Lyamsaev K.G., Severina I.I., Il’yasova T.M., Gulyaev M.V., Dedukhova V.I., Trendeleva T.A., Plotnikov E.Y., Zvyagilskaya R.A., Chernyak B.V., Zorov D.B., Antonenko Y.N., Skulachev V.P. 2014. A short-chain alkyl derivative of Rhodamine 19 acts as a mild uncoupler of mitochondria and a neuroprotector. Biochim. et Biophys. Acta (BBA) – Bioenerget. 1837 (10), 1739–1747. https://doi.org/10.1016/j.bbabio.2014.07.006

  42. Lei E.K., Kelley S.O. 2017. Delivery and release of small-molecule probes in mitochondria using traceless linkers. J. Amer. Chem. Soc. 139 (28), 9455–9458. https://doi.org/10.1021/jacs.7b04415

  43. Ripcke J., Zarse K., Ristow M., Birringer M. 2009. Small-molecule targeting of the mitochondrial compartment with an endogenously cleaved reversible tag. ChemBioChem. 10.(10), 1689–1696. https://doi.org/10.1002/cbic.200900159

  44. Pathak R.K., Marrache S., Harn D.A., Dhar S. 2014. Mito-DCA: A mitochondria targeted molecular scaffold for efficacious delivery of metabolic modulator dichloroacetate. ACS Chem. Biol. 9 (5), 1178–1187. https://doi.org/10.1021/cb400944y

  45. Battogtokh G., Choi Y.S., Kang D.S., Park S.J., Shim M.S., Huh K.M., Kang H.C. 2018. Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives. Acta Pharmaceutica Sinica B. 8 (6), 862–880. https://doi.org/10.1016/j.apsb.2018.05.006

  46. Dubinin M.V., Semenova A.A., Ilzorkina A.I., Penkov N.V., Nedopekina D.A., Sharapov V.A., Khoroshavina E.I., Davletshin E.V., Belosludtseva N.V., Spivak A.Yu, Belosludtsev K.N. 2021. Mitochondria-targeted prooxidant effects of betulinic acid conjugated with delocalized lipophilic cation F1. Free Radical Biol. and Medicine. 168, 55–69. https://doi.org/10.1016/j.freeradbiomed.2021.03.036

  47. Mojarad-Jabali S., Farshbaf M., Walker P.R., Hemmati S., Fatahi Y., Zakeri-Milani P., Sarfraz M., Valizadeh H. 2021. An update on actively targeted liposomes in advanced drug delivery to glioma. Int. J. Pharmaceutics. 602, 120645. https://doi.org/10.1016/j.ijpharm.2021.120645

  48. Turetskiy E.A., Koloskova O.O., Nosova A.S., Shilovskiy I.P., Sebyakin Y.L., Khaitov M.R. 2017. Physicochemical properties of lipopeptide-based liposomes and their complexes with siRNA. Biomed. Khim. 63 (5), 472–475. Russian. https://doi.org/10.18097/PBMC20176305472

  49. Liu P., Chen G., Zhang J. 2022. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules. 27 (4), 1372. https://doi.org/10.3390/molecules27041372

  50. Yamada Y., Akita H., Kamiya H., Kogure K., Yamamoto T., Shinohara Y., Yamashita K., Kobayashi H., Kikuchi H., Harashima H. 2008. MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. Biochim. et Biophys. Acta (BBA)-Biomembranes. 1778 (2), 423–432. https://doi.org/10.1016/j.bbamem.2007.11.002

  51. Yamada Y., Nakamura K., Abe J., Hyodo M., Haga S., Ozaki M., Harashima H. 2015. Mitochondrial delivery of coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver. J. Control. Release. 213, 86–95. https://doi.org/10.1016/j.jconrel.2015.06.037

  52. Yamada Y., Tabata M., Yasuzaki Y., Nomura M., Shibata A., Ibayashi Y., Taniguchi Y., Sasaki S., Harashima H. 2014. A nanocarrier system for the delivery of nucleic acids targeted to a pancreatic beta cell line. Biomaterials. 35 (24), 6430–6438. https://doi.org/10.1016/j.biomaterials.2014.04.017

  53. Yamada Y., Maruyama M., Kita T., Usami S.I., Kitajiri S.I., Harashima H. 2020. The use of a MITO-Porter to deliver exogenous therapeutic RNA to a mitochondrial disease’s cell with a A1555G mutation in the mitochondrial 12S rRNA gene results in an increase in mitochondrial respiratory activity. Mitochondrion. 55, 134–144. https://doi.org/10.1016/j.mito.2020.09.008

  54. Lu J., Li R., Mu B., Peng Y., Zhao Y., Shi Y., Guo L., Hai L., Wu Y. 2022. Multiple targeted doxorubicin-lonidamine liposomes modified with p-hydroxybenzoic acid and triphenylphosphonium to synergistically treat glioma. Eur. J. Med. Chem. 230, 114093. https://doi.org/10.1016/j.ejmech.2021.114093

  55. Thomas A.P., Lee A.J., Palanikumar L, Jana B., Kim K., Kim S., Ok H., Seol J., Kim D., Kang B.H., Ryu J.H. 2019. Mitochondrial heat shock protein-guided photodynamic therapy. Chem. Commun. (Camb.). 55 (84), 12 631–12 634. https://doi.org/10.1039/c9cc06411g

  56. Jiang L., Zhou S., Zhang X., Li C., Ji S., Mao H., Jiang X. 2021. Mitochondrion-specific dendritic lipopeptide liposomes for targeted sub-cellular delivery. Nature Comm. 12, 2390. https://doi.org/10.1038/s41467-021-22594-2

  57. Cao Z., Zhu W., Wang W., Zhang C., Xu M., Liu J., Feng S.T., Jiang Q., Xie X. 2014. Stable cerasomes for simultaneous drug delivery and magnetic resonance imaging. Int. J. Nanomedicine. 9, 5103–5116. https://doi.org/10.2147/IJN.S66919

  58. Gileva A., Sarychev G., Kondrya U., Mironova M., Sapach A., Selina O., Budanova U., Burov S., Sebyakin Y., Markvicheva E. 2019. Lipoamino acid-based cerasomes for doxorubicin delivery: Preparation and in vitro evaluation. Mater. Sci. Eng. C Mater. Biol. Appl. 100, 724–734. https://doi.org/10.1016/j.msec.2019.02.111

  59. Wang Y., Wang B., Liao H., Song X., Wu H., Wang H., Shen H., Ma X., Tan M. 2015. Liposomal nanohybrid cerasomes for mitochondria-targeted drug delivery. J. Mater. Chem. B. 3 (36), 7291–7299. https://doi.org/10.1039/c5tb01197c

  60. Damrongrak K., Kloysawat K., Bunsupa S., Sakchasri K., Wongrakpanich A., Taresco V., Cuzzucoli Crucitti V., Garnett M.C., Suksiriworapong J. 2022. Delivery of acetogenin-enriched Annona muricata Linn leaf extract by folic acid-conjugated and triphenylphosphonium-conjugated poly (glycerol adipate) nanoparticles to enhance toxicity against ovarian cancer cells. Int. J. Pharm. 618, 121636. https://doi.org/10.1016/j.ijpharm.2022.121636

  61. Wang Z., Sun C., Wu H., Xie J., Zhang T., Li Y., Xu X., Wang P., Wang C. 2021. Cascade targeting codelivery of ingenol-3-angelate and doxorubicin for enhancing cancer chemoimmunotherapy through synergistic effects in prostate cancer. Mater. Today Bio. 13, 100189. https://doi.org/10.1016/j.mtbio.2021.100189

  62. Wang H., Zhang F., Wen H., Shi W., Huang Q., Huang Y., Xie J., Li P., Chen J, Qin L., Zhou Y. 2020. Tumor- and mitochondria-targeted nanoparticles eradicate drug resistant lung cancer through mitochondrial pathway of apoptosis. J. Nanobiotechnol. 18 (1), 8. https://doi.org/10.1186/s12951-019-0562-3

  63. Xu Y., Wang S., Chan H.F., Liu Y., Li H., He C., Li Z., Chen M. 2017. Triphenylphosphonium-modified poly(ethylene glycol)-poly(ε-caprolactone) micelles for mitochondria-targeted gambogic acid delivery. Int. J. Pharm. 522 (1–2), 21–33. https://doi.org/10.1016/j.ijpharm.2017.01.064

  64. Wang J., Li B., Qiu L., Qiao X., Yang H. 2022. Dendrimer-based drug delivery systems: History, challenges, and latest developments. J. Biol. Eng. 16 (1), 18. https://doi.org/10.1186/s13036-022-00298-5

  65. Liang S., Sun C., Yang P., Ma P., Huang S., Cheng Z., Yu X., Lin J. 2020. Core-shell structured upconversion nanocrystal-dendrimer composite as a carrier for mitochondria targeting and catalase enhanced anti-cancer photodynamic therapy. Biomaterials. 240, 119850. https://doi.org/10.1016/j.biomaterials.2020.119850

  66. Johnson L.V., Walsh M.L., Chen L.B. 1980. Localization of mitochondria in living cells with rhodamine 123. Proc. Nat. Acad. Sci. USA. 77 (2), 990–994. https://doi.org/10.1073/pnas.77.2.990

  67. Summerhayes I.C., Lampidis T.J., Bernal S.D., Nadakavukaren J.J., Nadakavukaren KK, Shepherd E.L., Chen L.B. 1982. Unusual retention of rhodamine 123 by mitochondria in muscle and carcinoma cells. Proc. Nat. Acad. Sci. USA. 79 (17), 5292–5296. https://doi.org/10.1073/pnas.79.17.5292

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