Tailoring Crystallization Modulators for the Facile Synthesis of One‐Dimensional Covalent Organic Frameworks to Boost Ultrasound‐Triggered Pyroptosis and Immunotherapy

ABSTRACT Ultrasound (US)‐induced tumor cell pyroptosis holds great potential for cancer immunotherapy; however, its efficacy is often constrained by the inadequate reactive oxygen species (ROS) generation of conventional sonosensitizers. Herein, one‐dimensional porphyrin‐based covalent organic frameworks (designated as TD‐aniline and TD‐FeCl 3 ) with well‐defined structures were constructed under mild conditions via a novel synthesis strategy that employed aniline or FeCl 3 as crystallization modulators, thereby achieving efficient ROS generation and controllable activation of tumor cell pyroptosis. Notably, FeCl 3 not only promoted the ordered assembly of TD‐FeCl 3 but also introduced metal sites via coordination with porphyrin cores, resulting in superior sonodynamic performance compared to TD‐aniline. Specifically, metal coordination in TD‐FeCl 3 reduced its band gap to promote electron‐hole pair (e − –h + ) generation under ultrasound. Meanwhile, the introduced Fe 3+ diminished spatial e − –h + overlap in the excited state, thereby suppressing charge recombination, and ultimately channeling more excited‐state energy into a synergistic enhancement of superoxide anion and singlet oxygen production. Moreover, US irradiation enhanced the Fenton‐like activity of TD‐FeCl 3 . Based on its superior ROS generation capacity, TD‐FeCl 3 effectively promoted US‐triggered pyroptosis in tumor cells, leading to robust antitumor immune responses. This work establishes a novel paradigm for the controlled synthesis of one‐dimensional COFs and opens new avenues for pyroptosis‐based immunotherapy.