Emerging phototherapeutic roles of covalent organic frameworks in malignant cell ablation, wound healing, and...

Covalent organic frameworks (COFs) represent highly promising scaffolds for biomedical applications, notably in malignant cell ablation, infected wound healing, and antimicrobial phototherapies. Reticular design precisely controls the pore size, linkages, and dimensionality of COFs, enabling tailored functions such as pH/redox-responsive bonds. This review focuses on three application areas in which COFs have been most thoroughly investigated: phototherapeutic tumor ablation, antibacterial wound disinfection and biofilm disruption, and broader pathogen control. A key challenge in biomedical COF design is the simultaneous optimization of biocompatibility, hydrolytic stability, chemical stability under physiological conditions, colloidal dispersibility, and stimulus-responsive degradability, while also tuning crystallinity and surface area to balance high drug-loading capacity with safe, controlled release. Imine-linked COFs offer favorable pH- and redox-responsive behavior; they outperform more stable amide-, boron-, vinylene-, and triazine-linked analogues in stimulus-triggered release, but their moderate structural stability under physiological conditions requires innovative reticular design and post-synthetic modifications that preserve framework integrity without sacrificing stimulus-responsiveness. In photothermal therapy (PTT) and photodynamic therapy (PDT), reticularly designed COFs integrate intrinsic near-infrared (NIR)-absorbing chromophores (photothermal agents) or photosensitizers within their ordered pores; in parallel, COF-based composites act as carriers for external dyes (e.g., ICG) or inorganic photothermal materials (e.g., Fe₃O₄). Both strategies enable selective cancer cell ablation through hyperthermia-induced membrane disruption (>44 °C) for PTT and ROS-mediated oxidative damage for PDT. These mechanisms also extend to pathogen eradication in antimicrobial applications, where they promote accelerated infected-wound healing via biofilm disruption and tissue remodeling. Yet, nonselective ROS-mediated cytotoxicity and off-target thermal damage remain significant barriers. Recent progress in nanoscale COFs (nCOFs, 50-200 nm) and PEGylated, surface-engineered systems has improved dispersibility and biological barrier penetration, underscoring their potential as next-generation theranostic agents.