Tailoring Crystallization Modulators for the Facile Synthesis of One-Dimensional Covalent Organic Frameworks to Boost...

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.