Engineered covalent organic framework-based nanosystem for strengthening pyroptosis-mediated tumor immunotherapy.

Pyroptosis-based nanomedicine holds inspiring potential to transform "cold tumors" into "hot tumors" within the tumor immunosuppressive microenvironment, thus significantly advancing the progress of tumor immunotherapy. However, developing multifunctional and highly selective nanosystems capable of inducing pyroptosis remains a challenge. As emerging organic materials, covalent organic frameworks (COFs) possess adjustable chemical structures, excellent molecular loading capacities, and excellent biocompatibility, which enable them to serve as ideal therapeutic nanosystems, offering promising prospect for advancing pyroptosis-based tumor immunotherapy. In this review, the latest research developments on COF nanomedicine-based cell pyroptosis strategies for chemically regulating the tumor immune microenvironment and enhancing the therapeutic output of immunotherapy are systematically summarized. Specifically, we will discuss the structural diversity and cell pyroptosis-induced mechanism driven by the COF family, mainly focusing on a summary of either COFs alone or combined with other drugs to trigger cell pyroptosis. In addition, we systematically analyze the existing challenges in the structural design and functional integration of COF materials. Furthermore, we rationally envision the potential promoting effects of emerging interdisciplinary technologies on materials construction and biological evaluation, aiming to propose innovative chemical strategies to enhance the efficacy of COF-based cancer immunotherapy.