A Multifunctional Chitosan-Coated Ciprofloxacin–Luteolin Lipid Nanoplatform for Photodynamic Therapy of Prostatic Cancer

Abstract

This study developed chitosan (CS)-coated lipid nanoparticles (LNPs) co-loaded with CIP and LUT (CCIPLUTLNPs) as a multifunctional photodynamic therapy (PDT)-enhanced nanoplatform for PCA therapy. The formulations were characterized by particle size, polydispersity index, zeta potential, and encapsulation efficiency. Stability and hemocompatibility were also evaluated. Anticancer activity was assessed in PC-3 cells by measuring cell viability, intracellular reactive oxygen species (ROS) generation under dark and sunlight irradiation, and mitochondrial membrane potential (MMP). In addition, molecular docking was performed against 5α-reductase, androgen receptor (AR), and DNA topoisomerase IIα (TOP2A). Results: The developed LNPs exhibited nanoscale particle size, narrow size distribution, high drug encapsulation efficiency, and a positive surface charge following CS coating. The CS-coated LNPs demonstrated good storage stability and excellent hemocompatibility. Moreover, CCIPLUTLNPs produced the greatest cytotoxicity, enhanced ROS generation, and pronounced mitochondrial membrane depolarization in PC-3 cells. Sunlight irradiation significantly increased ROS production compared with dark conditions, confirming enhanced PDT activity. Molecular docking revealed favorable binding of CIP and LUT to 5α-reductase, AR, and TOP2A, supporting a multitarget anticancer mechanism. Conclusion: CCIPLUTLNPs represent a promising multifunctional nanoplatform that integrates efficient drug delivery, ROS-mediated PDT, and multitarget molecular interactions, offering a potential strategy for improved PCA treatment.