Freezing-ActivatedCovalent Organic Frameworks forPrecise Fluorescence Cryo-Imaging of Cancer Tissue

Cryosurgery represents a transformative approach in the treatment of resistant tumors, utilizing extreme cold to selectively ablate malignant tissue. However, the clinical success of this technique is constrained by the limited ability of current imaging techniques to differentiate effectively between cancerous and healthy tissues with high spatial resolution. To overcome this challenge, we present a nanoscale Covalent Organic Framework, nTG-DFP-COF, specifically designed to enhance fluorescence-guided cryo-imaging. This framework exhibits a unique temperature-dependent luminescence, that results in enhanced fluorescence emission under cryogenic conditions, enabling precise tissue differentiation during surgical procedures. Engineered for biocompatibility and water dispersibility, nTG-DFP-COF demonstrates minimal cytotoxicity and exceptional specificity toward cancer cells. Comprehensive in vitro, in vivo, and ex vivo evaluations confirm its structural stability and functional efficacy under cryogenic conditions. This innovation not only enhances the precision and safety of cryosurgical procedures but also advances the integration of diagnostic and therapeutic functionalities into a unified platform. By substantially improving tumor targeting accuracy, the use of nTG-DFP-COF will reduce the need for repeat surgeries, facilitate faster recovery, and minimize healthcare costs, thus setting a new standard in oncologic imaging and intervention.