Light-triggered controllable carbon monoxide (CO) release represents a promising approach for cancer therapy but is limited by the poor tissue penetration of light and insufficient CO release rates within deep tumor microenvironments. Herein, inspired by near-infrared (NIR)-activated multiphoton photocatalysis, a novel zinc-based metal-organic framework (ZnTBH) is reported, for the first time, to enable effective NIR-mediated synergistic therapy through combined CO gas therapy and photodynamic therapy (PDT) in deep-seated tumors. The engineered MOF integrates a V-shaped Tröger's base (TB) derivative with an A-π-A configuration as the organic linker, synergistically enhancing CO2 adsorption to overcome the "dilute CO2" challenge in tumors while enabling efficient endogenous CO2-to-CO conversion via NIR-driven multiphoton photocatalysis. Moreover, the photogenerated holes localize on biphenyl-4,4'-dicarboxylic acid can drive water oxidation to hydroxyl radicals (•OH), thereby further improving therapeutic efficacy. This study presents a significant advancement in the design of NIR light-driven photocatalytic systems for safe, precise, and localized CO delivery, offering new opportunities for CO-based or combination therapies in the treatment of deep-seated tumors.
Li et al. (Tue,) studied this question.