Recent Advances in Clinically Used and Trialed Photosensitizers for Antitumor Photodynamic Therapy

Photodynamic therapy (PDT) has gained significant attention as a minimally invasive cancer treatment that induces localized cytotoxicity with limited systemic side effects. When activated by light, typically in the visible or near-infrared spectrum, photosensitizers generate reactive oxygen species (ROS), leading to direct tumor cell death, vascular disruption, and stimulation of antitumor immune responses. This review provides an in-depth overview of the current understanding of PDT's antitumor mechanisms, focusing on ROS-induced cell death, immunogenic cell death, and tumor microenvironment modulation. Additionally, this review provides a critical evaluation of both clinically approved and investigational photosensitizers, detailing their chemical structures, photophysical properties, and therapeutic applications. We also discuss recent advances in combination strategies that integrate PDT with chemotherapy, radiotherapy, or immunotherapy to achieve enhanced therapeutic outcomes. Special emphasis is placed on emerging smart photosensitizers and tumor-targeted delivery systems that respond to microenvironmental stimuli, enhancing therapeutic precision and efficacy.