Smart covalent organic frameworks in cancer sensing and imaging: opportunities, challenges, and translational prospects.

Covalent organic frameworks (COFs) represent a rapidly expanding class of porous crystalline materials with exceptional potential in cancer diagnosis and therapy. Their ordered π-conjugated backbones, tunable pore architectures, and abundant functional sites provide unique advantages for drug loading, controlled release, and biointerfacing. Unlike conventional porous carriers, COFs exhibit intrinsic optical, electrical, and chemical properties that enable them to act both as delivery scaffolds and as active therapeutic platforms. Recent advances demonstrate their integration into drug delivery systems, photodynamic therapy (PDT), photothermal therapy (PTT), biosensing, and bioimaging. In cancer sensing and imaging, nanoscale COFs improve probe stability, enhance detection sensitivity, and enable responsive diagnostic platforms with reduced signal quenching. Furthermore, COFs can stabilize or directly function as photosensitizers and photothermal agents, thereby facilitating multimodal, imaging-guided therapeutic interventions. Despite these advances, key challenges remain, including scalable synthesis, long-term biocompatibility, precise drug-release control, and overcoming tumor heterogeneity. This review highlights emerging strategies to optimize COF stability, pore design, and functionalization, while exploring their potential applications across oncology. Finally, perspectives on clinical translation underscore the importance of interdisciplinary approaches to position COFs as next-generation platforms for precision cancer medicine, addressing urgent needs in early detection, therapeutic resistance, and metastasis management. Finally, the unique properties of COFs make them promising applicants for improving therapeutic products in cancer treatment.