A NTR and O2 programmed responsive photogenic radicals for efficient hypoxia cancer therapy

Stimulus responsive photodynamic therapy has attracted much attention. Although many methods have been proposed to alleviate the impact of hypoxia on photodynamic therapy (PDT), hypoxia is still one of the biggest obstacles to the efficient photodynamic treatment of tumors. Herein, a novel kind of nitroreductase (NTR) and O2 programmed responsive photosensitizer Eos-NO2 was developed to achieve precise and efficient PDT of hypoxia tumor. Specifically, the PDT "off" state Eos-NO2 was activated by the overexpressed NTR in tumor region to form PDT "on" state Eos. Then, the produced Eos in hypoxia could further generate the active free radicals and singlet oxygen for the efficient treatment of hypoxic tumors owing to photo-induced free radical process. Both in vitro and in vivo results confirm that such a NTR and O2 programmed responsive photosensitizer Eos-NO2 shows high specificity and selectivity for hypoxic solid tumor, presenting good prospects in the clinical cancer phototherapy.