Renal Clearable Catalytic 2D Au–Porphyrin Coordination Polymer Augmented Photothermal‐Gas Synergistic Cancer Therapy

Abstract As a gasotransmitter, carbon monoxide (CO) possesses antitumor activity by reversing the Warburg effect at higher concentrations. The targeted delivery of carbon monoxide‐releasing molecules (CORMs) using nanomaterials is an appealing option for CO administration, but how to maintain CO above the threshold concentration in tumor tissue remains a challenge. Herein, a nanozyme‐catalyzed cascade reaction is proposed to promote CO release for high‐efficacy photothermal therapy (PTT)‐combined CO therapy of cancer. A gold‐based porphyrinic coordination polymer nanosheet (Au⁰–Por) is synthesized to serve as a carrier for CORM. It also possesses excellent glucose oxygenase‐like activity owing to ultrasmall zero‐valent gold atoms on the nanosheet. The catalytically generated H₂O₂ can efficiently catalyze CORM decomposition, which enables in situ generation of sufficient CO for gas therapy. In vivo, the Au⁰–Por nanosheets‐enhanced photoacoustic imaging (PAI) and fluorescence imaging collectively demonstrate high tumor‐targeting efficiency and nanomaterial retention. Proven to have augmented therapeutic efficacy, the nanoplatform can also be easily degraded and excreted through the kidney, indicating good biocompatibility. Thus, the application of rational designed Au⁰–Por nanosheet with facile approach and biodegradable property to PAI‐guided synergistic gas therapy can provide a strategy for the development of biocompatible and highly effective gaseous nanomedicine.