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Nucleic acid aptamers increase the anticancer efficiency and reduce the toxicity of cisplatin-arabinogalactan conjugates in vivo / T. N. Zamay, A. K. Starkov, O. S. Kolovskaya [et al.] // Nucleic Acid Ther. - 2022. - Vol. 32, Is. 6. - P. 497-506, DOI 10.1089/nat.2022.0024. - Cited References: 42 . - ISSN 2159-3337. - ISSN 2159-3345
Кл.слова (ненормированные):
cisplatin -- aptamer -- arabinogalactan -- cancer chemotherapy -- ascites carcinoma
Аннотация: Cisplatin is an effective drug for treating various cancer types. However, it is highly toxic for both healthy and tumor cells. Therefore, there is a need to reduce its therapeutic dose and increase targeted bioavailability. One of the ways to achieve this could be the coating of cisplatin with polysaccharides and specific carriers for targeted delivery. Nucleic acid aptamers could be used as carriers for the specific delivery of medicine to cancer cells. Cisplatin-arabinogalactan-aptamer (Cis-AG-Ap) conjugate was synthesized based on Cis-dichlorodiammineplatinum, Siberian larch arabinogalactan, and aptamer AS-42 specific to heat-shock proteins (HSP) 71?kDa (Hspa8) and HSP 90-beta (Hsp90ab1). The antitumor effect was estimated using ascites and metastatic Ehrlich tumor models. Cis-AG-Ap toxicity was assessed by blood biochemistry on healthy mice. Here, we demonstrated enhanced anticancer activity of Cis-AG-Ap and its specific accumulation in tumor foci. It was shown that targeted delivery allowed a 15-fold reduction in the therapeutic dose of cisplatin and its toxicity. Cis-AG-Ap sufficiently suppressed the growth of Ehrlich's ascites carcinoma, the mass and extent of tumor metastasis in vivo. Arabinogalactan and the aptamers promoted cisplatin efficiency by enhancing its bioavailability. The described strategy could be very promising for targeted anticancer therapy.

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Держатели документа:
Laboratory for Digital Controlled Drugs and Theranostics, Federal Research Center "Krasnoyarsk Research Center" of the Siberian Branch of the Russian Academy of Science, Krasnoyarsk, Russian Federation
Laboratory For Biomolecular and Medical Technologies, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenecky, Krasnoyarsk, Russian Federation
Institute of Chemistry and Chemical Technology SB RAS, Federal Research Center "Krasnoyarsk Science Center SB RAS, Krasnoyarsk660036, Russian Federation
Department of Chemistry, Siberian Federal University, Krasnoyarsk, Russian Federation
Laboratory for Physics of Magnetic Phenomena, Kirensky Institute of Physics, Federal Research Center Krasnoyarsk Science Center SB RAS, Krasnoyarsk, Russian Federation
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada

Доп.точки доступа:
Zamay, T. N.; Starkov, A. K.; Kolovskaya, O. S.; Zamay, G. S.; Veprintsev, D. V.; Luzan, N.; Nikolaeva, E. D.; Lukyanenko, K. A.; Artyushenko, P. V.; Shchugoreva, I. A.; Glazyrin, Y. E.; Koshmanova, A. A.; Krat, A. V.; Tereshina, D. S.; Zamay, S. S.; Pats, Y. S.; Zukov, R. A.; Tomilin, F. N.; Томилин, Феликс Николаевич; Berezovski, M. V.; Kichkailo, A. S.
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