New guidelines and definitions for type I photodynamic therapy

The advent of photochemical technologies has revolutionized biology and medicine, offering groundbreaking innovations in cancer treatment and beyond. Among these, photodynamic therapy (PDT) has emerged as a promising approach to cancer therapy, leveraging cytotoxic reactive oxygen species (ROS) to eliminate cancer cells. While traditional type II PDT relies on high oxygen levels and consumes substantial amounts of oxygen, type I PDT requires less oxygen and holds great potential in addressing the hypoxic microenvironments characteristic of solid tumors. Over the last six years, our research team has made pioneering contributions to this field, with a particular focus on type I photosensitizers (PSs) and their diverse applications, including oxygen-sparing PDT, mitochondrial respiration inhibitors, modulation of cellular self-protection pathways, targeted cancer cell destruction, regulation of cellular signaling pathways, immune activation via nanomedicines, and intracellular oxygen-independent artificial photoredox catalysis. Notably, in 2018, our research proposed a "partial oxygen-recyclable mechanism" mediated by O2˙-, successfully revealing why the type I mechanism can be used for overcoming PDT hypoxia resistance. This revitalized interest in type I PDT and inspired numerous research groups worldwide to develop a plethora of new O2˙- photogenerators. However, inconsistencies in mechanistic interpretations, detection methodologies, and application strategies have arisen due to fragmented communication within the field of photoscience and ambiguity in some key definitions. Given our research team's significant contributions and expertise in the type I PDT domain, we believe it is imperative to present a comprehensive review to establish standardized definitions, mechanisms, molecular designs, detection techniques, and clinical applications of type I PDT in cancer diagnosis and treatment. Our goal is to provide a clear and authoritative resource for both specialists and non-specialists, fostering a deeper understanding of type I PDT and inspiring future innovations to advance more effective and clinically relevant therapies for cancer treatment.