Near‐Infrared‐Activated Multiphoton Photocatalytic System for Synergistic Therapy via CO Generation and •OH Production

Abstract

ABSTRACT 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 CO 2 adsorption to overcome the “dilute CO 2 ” challenge in tumors while enabling efficient endogenous CO 2 ‐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.