Intermolecular Electron Transfer: Toward a General Photochemical Engine for Type I Photodynamic Therapy.

Hypoxia is an intrinsic characteristic within tumors or infected tissues, which poses a significant barrier to effective photodynamic therapy (PDT). Type I PDT is a promising complement or alternative to conventional Type II PDT owing to its reduced or absent reliance on molecular oxygen. Type I photosensitizers (PSs) are essential to Type I PDT, which undergoes photoinduced electron transfer with biological substrates to produce cytotoxic radical species (O •, •OH) for the targeted destruction of pathological tissues. However, the limited mechanistic understanding of photoinduced electron transfer makes the rational design of Type I PSs a great challenge. Encouragingly, compelling evidence reveals that intermolecular electron transfer (InterET) is not an obscure mechanism, but rather the predominant photochemical engine driving Type I PDT. This Perspective reviews the evolution and challenges of InterET in Type I PDT, with a particular focus on semiempirical design principles for InterET-based Type I PSs. Finally, it is concluded with an outlook on future opportunities and remaining challenges in the development of next-generation Type I PSs.