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

Abstract

Singlet oxygen (¹ O₂ ) has a potent anticancer effect, but photosensitized generation of ¹ O₂ 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 O₂ -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 MoO₄^2- catalyst and alkaline sodium carbonate within liposomes, which offers a favorable pH condition for MoO₄^2- -catalyzed generation of ¹ O₂ from H₂ O₂ and protects MoO₄^2- from GSH chelation owing to the impermeability of liposomal lipid membrane to ions and GSH. H₂ O₂ and ¹ O₂ can freely cross the liposomal membrane, allowing CMTN with a built-in NIR-II ratiometric fluorescent ¹ O₂ sensor to achieve monitored tumor CDT.

Keywords: NIR-II ratiometric fluorescence; catalytic microenvironment; chemodynamic therapy; nanoreactors; singlet oxygen.