Dual Functions of Riboflavin-functionalized Poly(lactic-co-glycolic acid) Nanoparticles for Enhanced Drug Delivery Efficiency and Photodynamic Therapy in Triple-negative Breast Cancer Cells

Combating triple-negative breast cancer (TNBC) is one of the greatest challenges in cancer therapy. This is primarily due to the difficulties in developing drug delivery systems that can effectively target cancer sites. In this study, we demonstrated a proof-of-principle concept using modified surfaces of poly(lactic-co-glycolic acid) nanoparticles linked with a riboflavin analogue (PLGA-CSRf) to obtain a dual-functional material. PLGA-CSRf nanoparticles were able to function as a drug delivery ligand and a photodynamic therapy agent for TNBC cells (MDA-MB-231). Biocompatibility of novel PLGA-CSRf nanoparticles was evaluated with both breast cancer and normal breast (MCF-10A) cells. In vitro studies revealed a six-fold increase in the cellular uptake of PLGA-CSRf nanoparticles in cancer cells compared with normal cells. The results demonstrate the ability of riboflavin (Rf) to enhance the delivery of PLGA nanoparticles to TNBC cells. The viability of TNBC cells was decreased following treatment with doxorubicin-encapsulated PLGA-CSRf nanoparticles in combination with UV irradiation, due to the photosensitizing property of Rf on the surface of the nanoparticles. This work demonstrated the ability of PLGA-CSRf to function both as an effective drug delivery carrier and as a therapeutic entity, with the potential to enhance photodynamic effects in the highly aggressive TNBC model.