A new perspective on intracellular redox environment-mediated innovative photodynamic therapy

Thanks to its non-invasiveness and spatiotemporal manipulation in the treatment process and low drug resistance in comparison to chemotherapy, photodynamic therapy (PDT) has been developed to the forefront of tumour therapies. Particularly, PDT activated or driven by the intracellular redox environment attracts increasing attention. In this review, we present our efforts on this theme in the past five years, including (1) in-mitochondria synthesis of cyanine-based photosensitizers (PSs); (2) glutathione (GSH) participating PS activation via a cascade reaction; and (3) GSH or 1,4-dihydronicotinamide adenine dinucleotide (NADH) driven reductive PDT (rPDT). Additionally, the emergent concepts, molecular designs and photochemical mechanisms are also discussed in detail. Finally, we provide an outlook on future progression to better meet the requirements for clinical applications. We hope that the new perspective on intratumoural redox environment-responsive PDT will inspire further development of advanced phototherapies like rPDT.