Screening Metal Ions to Tailor Carrier Dynamics in Porphyrin‐Based Covalent Organic Polymers for Enhanced Sonocatalytic Pyroptosis and Immunotherapy

Abstract Precise induction of tumor pyroptosis represents an effective strategy to potentiate antitumor immune responses; however, it still confronts challenges such as insufficient spatiotemporal controllability and restricted generation of effector molecules like reactive oxygen species (ROS). In this study, we developed a metal‐doped covalent organic polymer (COP) sonosensitizer platform that overcame the constraints of the tumor hypoxic microenvironment on ROS generation through systematic modulation of carrier dynamics by six metal ions (Mn 2+ , Fe 3+ , Co 2+ , Ni 2+ , Cu 2+ , and Zn 2+ ), enabling efficient and controllable ultrasound‐driven induction of tumor cell pyroptosis. Systematic screening established Co‐doped COP (PA‐Co) as the optimal system, demonstrating superior carrier separation. The performance enhancement originated from the unique ability of cobalt doping to synergistically optimize band structures, redistribute charges, and reduce exciton binding energy, thereby decreasing the spatial overlap of electron‐hole pairs while extending their centroid separation distances. Under ultrasound irradiation, PA‐Co enhanced both the electron transfer pathway and Fenton‐like processes, efficiently generating superoxide anions and hydroxyl radicals to elevate ROS levels in hypoxic microenvironments, thereby inducing tumor cell pyroptosis and activating robust immune response. This work not only provides fundamental insights into metal ion‐modulated carrier dynamics in sonosensitizers but also offers a strategy for activating antitumor immunity through controllable pyroptosis.