Organelle-targeted small molecular photosensitizers for enhanced photodynamic therapy: a minireview for recent advances and potential applications

Abstract

Photodynamic therapy (PDT) is a promising approach for cancer treatment that involves the use of photosensitizers to generate reactive oxygen species upon light irradiation, resulting in selective cytotoxicity. To enhance the efficiency of PDT, researchers have developed organelle-targeting photosensitizers that specifically accumulate in critical cellular organelles. This review provides a comprehensive overview of recent advancements in the development of organelle-targeting photosensitizers for PDT. Different organelles, including mitochondria, plasma membrane, lysosome, endoplasmic reticulum, lipid droplets, nucleus, and Golgi, have been targeted to improve the selectivity and effectiveness of PDT. Various strategies have been employed to design and synthesize these photosensitizers, optimizing their organelle-specific accumulation and photodynamic efficiency. This review discusses the principles and mechanisms underlying the design of organelle-targeting photosensitizers, along with their exceptional results achieved in preclinical studies. Furthermore, potential applications and challenges in the development of multi-organelles-targeting photosensitizers and the synergistic use of multiple photosensitizers targeting different organelles are highlighted. Overall, organelle-targeting photosensitizers offer a promising avenue for advancing the field of PDT and improving its clinical applicability.