Design, in silico modelling and functionality theory of folate-receptor-targeted myricetin-loaded bovine serum albumin nanoparticle formulation for cancer treatment

Abstract

Targeted drug delivery systems are a promising field of research. Nano-engineered material-mediated drug delivery possesses remarkable potential for the treatment of various malignancies. Here, folic acid (FA)-conjugated bovine serum albumin (BSA) nanoparticles (NPs) were used to encapsulate myricetin (Myr). Subsequently, the delivery of Myr via naturally overexpressed folate receptor (FR) to FR-positive breast cancer cells was studied. Myr-loaded BSA NPs were assembled by modified desolvation cross-linking technique. An FA-conjugated carrier, N-hydroxysuccinimide (NHS)-FA ester, was successfully synthesized. Its functional and structural characteristics were confirmed by ultraviolet, Fourier-transform infrared, and proton nuclear magnetic resonance spectroscopy. Biocompatible FA-conjugated, Myr-loaded BSA NPs (FA-Myr-BSA NPs) were successfully formulated using a carbonate/bicarbonate buffer. Their morphology, size, shape, physiological stability, and drug release kinetics were studied. Molecular docking studies revealed that FA-Myr-BSA NPs readily bound non-covalently to folate receptors and facilitated active drug endocytosis. FA-Myr-BSA NPs could trigger fast release of Myr in an acidic medium (pH 5.4), and showed high biocompatibility in a physiological medium. FA-Myr-BSA NPs effectively decreased the viability of MCF-7 cells after 24 h with 72.45 μg ml−1 IC50 value. In addition, FA-Myr-BSA NPs enhanced the uptake of Myr in MCF-7 cells. After incubation, a typical apoptotic morphology of condensed nuclei and distorted membrane bodies was observed. The NPs also targeted mitochondria of MCF-7 cells, significantly increasing reactive oxygen species release and contributing to the loss of mitochondrial membrane integrity. The observed results confirm that the newly developed FA-Myr-BSA NPs can serve as a potential carrier for Myr to increase the anticancer activity of this chemotherapeutic.