Engineered Covalent Organic Frameworks-based Nanosystem for Strengthening Pyroptosis-Mediated Tumor Immunotherapy

Abstract

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