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0220U104539,
0120U105520
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Molecular design, creation, in vitro and in vivo screening of nanocomplexes of natural alkaloids with C60 fullerene to increase the effectiveness of metastatic cancer therapy
Matyshevska Olha P., Доктор біологічних наук
22-12-2020
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine
It was established that the use of the strategy of non-covalent complexation of berberine (Ber) with fullerene nanostructure C60 allows to increase the effectiveness of the toxic effect of alkaloid on lung carcinoma cells LLC both in vitro and in vivo. Berberine in free form and C60 nanocomplexes with 1: 2, 1: 1 and 2: 1 molar ratio of components at Ber-equivalent concentration were used in the experiments. It was found that the treatment of LLC cells with C60-Ber nanocomplexes led to faster intracellular absorption of the alkaloid, its much greater accumulation in cells and more powerful than when treated with berberine in free form, cytotoxic effect, which was subject to the following sequence: free 1 Ber <1: : 1 <2: 1 nanocomplex C60-Ber. In the case of nanocomplex C60-Ber 2: 1 using, it was possible to significantly reduce the effective dose (21.3-fold decrease at the value of IC50) of berberine. The detected activation of caspase 3/7 by the action of the nanocomplex indicates the induction of cell death by the mechanism of apoptosis. Under action of C60-Ber 2: 1 nanocomplex on LLC cells, inhibition of migration and invasive potential, reduction of mRNA expression of markers of epithelial-mesenchymal transition, Ruk/CIN85 and Zeb1 were demonstrated. Analysis of the expression of genes inherent in cancer stem cells (CSCs) showed that the action of berberine significantly reduces the expression of CD44 and increases the expression of CD24. The Lewis lung carcinoma model demonstrated higher tumor growth inhibition efficacy than free berberine. The obtained data show that non-covalent complexation of berberine with fullerene C60 is a promising approach to optimizing the targeted delivery of the alkaloid and enhancing its antitumor action.
Hrabovskyi Olehovych, Oleksii O.
2020-12-22
Updated: 2025-12-08
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