A Novel Water-Soluble C60 Fullerene-Based Nano-Platform Enhances Efficiency of Anticancer Chemotherapy View Full Text


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Chapter Info

DATE

2021-09-12

AUTHORS

Yuriy Prylutskyy , Olga Matyshevska , Svitlana Prylutska , Anna Grebinyk , Maxim Evstigneev , Sergii Grebinyk , Larysa Skivka , Vsevolod Cherepanov , Anton Senenko , Rostyslav Stoika , Uwe Ritter , Peter Scharff , Thomas Dandekar , Marcus Frohme

ABSTRACT

Noncovalent water-soluble nanocomplexes of C60 fullerene (C60) with chemotherapeutic drugs (Doxorubicin (Dox), Cisplatin (Cis), and herbal alkaloid Berberine (Ber)) were created. Their anticancer action toward various tumor cells was studied in vitro, addressing specifically their biological synergy, compared with the action of these drugs in the non-immobilized form. Different theoretical and experimental (SEM and AFM microscopy, UV-Vis, DLS, NMR and SANS spectroscopy, ITC calorimetry) methods were applied for getting insight into the nature of the nanocomplexes with drug molecules, as well as into the physical forces enabling stabilization of these complexes. Physicochemical mechanisms were proposed for drug interaction with C60.An enhancement of the toxic action of the created water-soluble C60-drug nanocomplexes toward cancer cells, compared to the action of free drug, was found. Specifically, the C60-Dox nanocomplexes demonstrated ~3.5 higher cytotoxic potential in the leukemic cell lines (CCRF-CEM, Jurkat, THP1, and Molt-16) in comparison with free Dox in the nanometer range of concentrations. Besides, C60 doubled the intracellular level of the up-taken Dox, which also evidenced its function as a nanocarrier. The toxic effect of C60-Cis nanocomplex toward Lewis lung carcinoma (LLC) cells was shown to be higher with IC50 values 3.3 and 4.5 times at 48 h and 72 h, respectively, as compared to the IC50 of free drug. 12.5 μМ Cis had no effect on LLC cells’ viability. The C60-Cis nanocomplex in Cis-equivalent concentration substantially decreased the viability of tumor cells, impaired their shape and adhesion, inhibited migration, and induced their accumulation in the pro-apoptotic sub-G1 phase of cell cycle. An induction of apoptosis by the C60-Cis nanocomplex was confirmed by the activation of caspase 3/7 and externalization of phosphatidylserine on the outer membrane of LLC cells after their double staining with the Annexin V-FITC/PI. The complexation with C60 promoted intracellular uptake of the Ber. An increase in C60 concentration in the C60-Ber nanocomplexes was accompanied by the elevation of their antiproliferative potential toward CCRF-CEM cells in the order: free Ber ˂ 1:2 ˂ 1:1 ˂ 2:1.These findings suggest a universal potential of water-soluble pristine C60 as a unique nano-platform for the delivery of the chemotherapeutic drugs in cytotoxic effect of these drugs. More... »

PAGES

59-93

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/978-3-030-76235-3_3

DOI

http://dx.doi.org/10.1007/978-3-030-76235-3_3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1141059385


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