Photochemical Synergistic Treatment of Extrahepatic Cholangiocarcinoma Based on Nanomedicines Loaded with Hydroxy-camptothecin and AIE Photosensitiser

Photodynamic therapy (PDT) can effectively improve the survival and quality of life of patients with unresectable extrahepatic cholangiocarcinoma, but meanwhile, our previous study found that incompletely eradicated cholangiocarcinoma cells could re-proliferate due to the activation of the hypoxia-mediated HIF-1α signaling pathway and the intracellular antioxidant system following PDT. Therefore, in this study, we developed a glutathione-responsive targeted nanosystem (TSH NPs) consisting of a disulfide bond linking the photosensitiser TPA-Ph-RDN with aggregation-induced luminescence properties and the cholangiocarcinoma chemotherapeutic drug hydroxycamptothecin(HCPT). This nanosystem enhances the efficacy of PDT by leveraging the unique mechanism of HCPT, which not only exerts its chemotherapeutic effects on cholangiocarcinoma but also directly inhibits the HIF-1α-mediated signaling pathway, thereby achieving a "killing two birds with one stone" therapeutic strategy. Furthermore, the nanosystem demonstrated significant anti-cancer effects in both in vitro and in vivo experiments, offering a promising approach for the clinical treatment of patients with extrahepatic cholangiocarcinoma.