Covalent organic frameworks in cancer nanomedicine: Design principles, theranostic applications, and emerging cuproptosis-driven mechanisms

초록

Numerous types of nanostructures have been explored for cancer therapy and diagnosis, each providing distinct benefits. This has intensified efforts to develop more effective platforms for cancer detection and treatment. Recently, Covalent organic frameworks (COFs)-based nanostructures have been studied extensively within the biomedical area, mainly for their application in breast cancer treatment and diagnosis. COFs are crystalline, porous organic polymers assembled from diverse building units via covalent linkages, enabling rational control over framework composition, pore architecture, and functionality. Key advantages of COF-based nanostructures include high specific surface area and ordered nanochannels for efficient cargo loading, modular pre- and postsynthetic functionalization, and robust chemical/thermal stability. The following article contains a review of the structural properties of COF-based nanostructures, along with a summary of recent studies highlighting how these COFs have been used to improve the functionality of diagnostic and therapeutic agents. To our knowledge, this review is among the first to focus specifically on COF-based nanostructures designed to regulate intracellular copper homeostasis and selectively induce cuproptosis for cancer therapy. In particular, this article highlights recent advances in using COFs to induce cuproptosis, a newly described programmed cell-death process triggered by intracellular copper accumulation, for breast cancer intervention. Finally, this article evaluates the presentday challenges and limitations that exist for COF-based nanostructures when being used for breast cancer diagnosis and treatment, including aqueous stability, biodegradation/biosafety, particle-size control, and scalability.

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