Enhanced delivery of retinoic acid to breast cancer cells by folate receptor- targeted folic acid-conjugated glutenin nanoparticles for promising treatment of breast cancer

Abstract

Abstract Targeted delivery via surface receptors can significantly improve the therapeutic efficacy and reduce the adverse drug reactions. The protein nanocarrier system offers many advantages, such as encapsulation in various drugs and molecules and prolonged circulation. Here, the folate receptor-targeted folic acid-conjugated retinoic acid-loaded glutenin nanoparticles (FA-RA-Glu NPs) were successfully synthesised for enhanced delivery of retinoic acid to breast cancer cells (MCF-7). After a complete physico-chemical characterisation of FA-RA-Glu NPs, stability, drug release, release kinetics, cytotoxicity, apoptosis, cell death, and nucleic acid fragmentation were analysed. The results showed that FA-RA-Glu NPs were ⁓185 nm in size, predominantly spherical in shape, crystalline in nature and had a zeta potential of − 3 mV. The RA encapsulation efficiency and loading capacity of Glu NPs were 83.537% ± 3.32% and 9.917 ± 1.68%, respectively. The effects of FA-RA-Glu NPs against MCF-7 cells significantly reduced the number of viable cells and the induction of apoptosis. The cellular uptake study showed that the FA-RA-Glu NPs had facilitated endocytosis and delivered RA into MCF-7 cells. After treatment with FA-RA-Glu NPs, contracted nuclei and deformed membrane bodies were observed as typical apoptotic morphological changes. The released RA also targeted the mitochondria of MCF-7 cells, which significantly increased the levels of reactive oxygen species and contributed to the damage of mitochondrial membrane integrity. These results suggest that FA-RA-Glu NPs with facilitated endocytosis and targeted delivery of RA into MCF-7 cells may have significant therapeutic potential for the treatment of breast cancer.