4.7 Article

Protein-Mineral Composite Particles with Logarithmic Dependence of Anticancer Cytotoxicity on Concentration of Montmorillonite Nanoplates with Adsorbed Cytochrome c

Journal

PHARMACEUTICS
Volume 15, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/pharmaceutics15020386

Keywords

cytochrome c; montmorillonite; static light scattering; electric light scattering; microelectrophoresis; protein adsorption; in vitro anticancer cytotoxicity; cancer cell culture

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Montmorillonite (MM) colloid nanoplates are effective carriers for drug delivery due to their high adsorption capacity. By adsorbing the mitochondrial protein cytochrome c (cytC) onto MM plates, the composite cytC-MM particles exhibit anticancer properties when phagocytized by cancer cells, leading to apoptosis and cell death. This study investigated the physicochemical properties of cytC-MM particles at different cytC concentrations and found a linear relationship between cytotoxicity and particle concentration, with a cytotoxicity reaching 97%.
Montmorillonite (MM) colloid nanoplates have high adsorption capacity due to their large size/thickness ratio, which allows them to be used as carriers for drug delivery. Upon adsorption of the mitochondrial protein cytochrome c (cytC) onto MM plates, the composite cytC-MM particles acquire anticancer properties because of the ability of cancer cells to phagocytize submicron particles (in contrast to the normal cells). In this way, exogenous cytC can be introduced into tumor cells, thereby triggering apoptosis-an irreversible cascade of biochemical reactions leading to cell death. In the present study, we investigated the physicochemical properties of cytC-MM particles as a function of the cytC concentration in the suspension, namely, the electrophoretic mobility, the mass increment of MM monoplates upon cytC adsorption, the ratio of the adsorbed to the free cytC in the bulk, the protein density on the MM's surface, the number of cytC globules adsorbed on an MM monoplate, the concentration of cytC-MM composite particles in the suspension, and the dependence of cytotoxicity on the cytC-MM particle concentration. For this purpose, we used microelectrophoresis, static and electric light scattering, and a colon cancer cell culture to test the cytotoxic effects of the cytC-MM suspensions. The results show that the cytotoxicity depends linearly on the logarithm of the particle concentration in the cytC-MM suspension reaching 97%.

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