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

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-FeCl3) with well-defined structures were constructed under mild conditions via a novel synthesis strategy that employed aniline or FeCl3 as crystallization modulators, thereby achieving efficient ROS generation and controllable activation of tumor cell pyroptosis. Notably, FeCl3 not only promoted the ordered assembly of TD-FeCl3 but also introduced metal sites via coordination with porphyrin cores, resulting in superior sonodynamic performance compared to TD-aniline. Specifically, metal coordination in TD-FeCl3 reduced its band gap to promote electron-hole pair (e--h+) generation under ultrasound. Meanwhile, the introduced Fe3+ 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-FeCl3. Based on its superior ROS generation capacity, TD-FeCl3 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.