Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment

In continuation of our previous studies, we developed polymeric epigallocatechin 3-gallate (EGCG)-loaded nanoparticles (NPs) coupled with folic acid (FA), able to dually bind the human folate receptor alpha (FOLR1), and prostate-specific membrane antigen (PSMA+) in prostate cancer (PCa) model. After a preliminary computational molecular recognition of NP′ ligand binding on the FOLR1 active site, we synthesized the biocompatible block-copolymer PLGA-PEG-FA to prepare EGCG-targeted NPs (EGCG-T-NPs). The obtained NPs were characterized by various analytical techniques, and anticancer efficacy was determined by different sets of experiments in a 3D culture of PCa using PC3 and 22Rv1 cell lines. Results showed a significant reduction in spheroid size by EGCG-T-NPs, especially in PSMA+ (22Rv1) cells. The targeted NPs significantly enhanced the antiproliferative activity of EGCG against PCa cell lines, especially toward the PSMA+ cells, known to have higher FOLR1 expression. We did not observe any changes in the reactive oxygen species formation in both studied cell lines. However, significant changes in mitochondrial depolarization (15%) and polarization (18%) were recorded in response to EGCG-T-NP compared to control in 22Rv1. Similarly, EGCG-T-NP treatment also showed an increase in the number of dead apoptotic cells in 22Rv1 spheroids. Collectively, the obtained results support our hypothesis about the role of these targeted nanoprototypes in the increasing cellular uptake of EGCG payload into PCa cells, thus enhancing its antitumor efficacy.