Singlet Oxygen Generation in Dark-Hypoxia by Catalytic Microenvironment-Tailored Nanoreactors for NIR-II Fluorescence-Monitored Chemodynamic Therapy

Singlet oxygen (O-1(2)) has a potent anticancer effect, but photosensitized generation of O-1(2) is inhibited by tumor hypoxia and limited light penetration depth. Despite the potential of chemodynamic therapy (CDT) to circumvent these issues by exploration of O-1(2)-producing catalysts, engineering efficient CDT agents is still a formidable challenge since most catalysts require specific pH to function and become inactivated upon chelation by glutathione (GSH). Herein, we present a catalytic microenvironment-tailored nanoreactor (CMTN), constructed by encapsulating MoO42- catalyst and alkaline sodium carbonate within liposomes, which offers a favorable pH condition for MoO42--catalyzed generation of O-1(2) from H2O2 and protects MoO42- from GSH chelation owing to the impermeability of liposomal lipid membrane to ions and GSH. H2O2 and O-1(2) can freely cross the liposomal membrane, allowing CMTN with a built-in NIR-II ratiometric fluorescent O-1(2) sensor to achieve monitored tumor CDT.