AIEgens-driven photodynamic therapy:translational prospects and challenges in oncologyOA

Photodynamic therapy(PDT),as a clinically approved treatment modality,has attracted considerable attention in recent years due to its remarkable advantages.These include not only non-invasiveness,high spatiotemporal controllability,negligible drug resistance,and the potential for integration with optical diagnostics in theranostics[1],but also significantly reduced recovery times and lower treatment costs compared to conventional anticancer therapies such as surgery,chemotherapy,and radiotherapy[2].However,the overall theranostic efficacy of conventional FDA-approved photosensitizers(e.g.,porphyrin derivatives)is severely constrained by several inherent limitations,including limited penetration depth of the light source,a strong dependence on oxygen within the hypoxic tumor microenvironment(TME),high susceptibility to photobleaching,aggregation-induced quenching,as well as inevitable phototoxic damage to normal tissues during irradiation[3].In addition,the safety issues including eliciting pain or burning sensations[4],allergic reactions[5],and genotoxicity ascribed to DNA oxidative damage and breaks[6]must be addressed.This highlights the gap between promising lab results and real-world clinical application,as well as the key obstacles that must be tackled for broad clinical deployment(Figure 1A).