REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicThe Role of Nano-Therapeutics in Precision Cancer MedicineView all 4 articles
Covalent organic frameworks for cancer immunotherapy: mechanisms, applications, and prospects
Provisionally accepted
- 1Nantong University, Nantong, China
- 2Danyang People's Hospital of Jiangsu Province, Danyang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Covalent organic frameworks (COFs) have emerged as promising candidates in cancer immunotherapy, owing to their tunable pore structures, versatile functionality, and favorable biocompatibility. This review systematically highlights recent advances in COF-based materials that enhance immunotherapeutic efficacy through multiple strategies. Particular emphasis is placed on functionalized COFs for remodeling the immunosuppressive tumor microenvironment, by alleviating hypoxia and depleting glutathione, and their role as core sensitizers in various therapeutic modalities, including photodynamic, sonodynamic, radiotherapy, and chemodynamic therapy, to efficiently trigger immunogenic cell death (ICD). In addition, we comprehensively summarize how strategic structural engineering enhances phototherapeutic efficacy. This includes modulating the metal ions incorporated into the COF, controlling COF stacking modes, and adjusting the planarity or conformational twist of the building units to precisely tune bandgap energy and light absorption properties, thereby promoting stronger ICD induction. Furthermore, COFs serve as intelligent delivery platforms capable of controlled release of immune adjuvants and checkpoint inhibitors. The discussion also extends to cutting-edge applications, such as imaging-guided therapy, induction of tertiary lymphoid structure (TLS) formation, and activation of abscopal effects. These developments discussed in this review underscore the immense potential of COFs as multifunctional nanoplatforms in advancing effective and precise combination cancer immunotherapy. The insights provided in this review offer valuable reference for the biomedical applications of COFs, particularly in the integrated development of multimodal therapies and immunotherapy.
Keywords: cancer immunotherapy, covalent organic frameworks, Immunogenic cell death, immunosuppressive tumor microenvironment, Photodynamic therapy
Received: 05 Oct 2025; Accepted: 15 Dec 2025.
Copyright: © 2025 Zheng, Zou, Chen, Chen and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaohua Zheng
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.