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

Abstract Singlet oxygen ( 1 O 2 ) has a potent anticancer effect, but photosensitized generation of 1 O 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 1 O 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 MoO 4 2− catalyst and alkaline sodium carbonate within liposomes, which offers a favorable pH condition for MoO 4 2− ‐catalyzed generation of 1 O 2 from H 2 O 2 and protects MoO 4 2− from GSH chelation owing to the impermeability of liposomal lipid membrane to ions and GSH. H 2 O 2 and 1 O 2 can freely cross the liposomal membrane, allowing CMTN with a built‐in NIR‐II ratiometric fluorescent 1 O 2 sensor to achieve monitored tumor CDT.