Genistein loaded in self-assembled bovine serum albumin nanovehicles and their effects on mouse mammary adenocarcinoma cells

Abstract

Antitumor activity of plant-derived flavonoids has been researched during recent decades. Among them, genistein (Gen) stands out for showing cytotoxic activity against breast cancer cells. However, its low water solubility, limited bioavailability, and fast metabolism hinder its administration in chemopreventive therapies. To overcome these obstacles, bovine serum albumin nanovehicles (BSAnp) were obtained by a heat-induced self-assembly process at 70 °C and two aqueous medium pH (9.0 and 11.0) and assayed for the Gen loading. Thus, in this work, Gen loading in BSAnp was studied by spectroscopic techniques and compared with the one obtained for its stereoisomer, chrysin (Chrys). Results revealed that Gen binds to BSAnp via fluorescence quenching mechanism forming inclusion complexes. Compared to Chrys, Gen binding to BSAnp involved more molecules, whereas the association constant was similar for both flavonoids. In general, flavonoid loading in protein systems was strongly affected by the combined effects of BSA conformational state (native vs. aggregated), nanovehicle size, and flavonoid chemical structure. To evaluate the antitumor properties freeze-dried powders were obtained, and they were assayed in vitro after reconstitution by XTT technique and Annexin V-FITC flow cytometry against mouse mammary adenocarcinoma F3II cells. Gen-loaded BSAnp produced a significant decrease in cell viability compared with unloaded BSAnp systems, being the highest cytotoxic effects found for the lowest sized Gen-loaded BSAnp. The leading cytotoxicity mechanism for Gen-loaded systems was apoptosis. Summarizing, it can be concluded that BSAnp constitute versatile nanovehicles for potential flavonoid incorporation in pharmaceutical and nutraceutical matrices.