Benzo[a]phenoselenazine-based NIR photosensitizer for tumor-targeting photodynamic therapy via lysosomal-disruption pathway

The ultimate goal of cancer therapy is to develop antitumor agents that will destroy selectively tumor cells while sparing the health cell of the patient. Herein, we reported a novel tumor-specific and lysosome dual-targeted NIR photosensitizer, Se-Biotin, by conjugating a biotin ligand into benzo[a]phenoselenazinium derivative dye for selective destruction of tumor cells. Attractively, co-culture model showed that Se-Biotin could selectively target to and retain in biotin receptor-overexpressed tumor cells, which as a result significantly minimized the side effects toward normal cells. As confirmed by the in vitro anticancer mechanism, after cellular internalization, upon irradiation, the effective1O2 generation (ΦΔ = 0.69)severely disrupted the lysosomalintegrity and subsequently led to apoptotic cell death. Benefiting from these merits, Se-Biotin successfully achieved a superior anticancer performance with the IC50 as low as 85 nM, only under a low light dose irradiation (12 J/cm2, 660 nm). Therefore, these result demonstrated that Se-Biotin will be a promising PDT agent for targeted cancer photodynamic therapy.