cRGD-Peptide Modified\nCovalent Organic Frameworks\nfor Precision Chemotherapy in Triple-Negative Breast Cancer

This study presents the use of nanoscale covalent organic\nframeworks\n(nCOFs) conjugated with tumor-targeting peptides for the targeted\ntherapy of triple-negative breast cancer (TNBC). While peptides have\npreviously been used for targeted delivery, their conjugation with\nCOFs represents an innovative approach in this field. In particular,\nwe have developed alkyne-functionalized nCOFs chemically modified\nwith cyclic RGD peptides (Alkyn-nCOF-cRGD). This configuration is\ndesigned to specifically target α<sub>v</sub>β<sub>3</sub> integrins that are overexpressed in TNBC cells. These nCOFs exhibit\nexcellent biocompatibility and are engineered to selectively disintegrate\nunder acidic conditions, allowing for precise and localized drug release\nin tumor environment. Doxorubicin, a chemotherapeutic agent, has been\nencapsulated in these nCOFs with high loading efficiency. The therapeutic\npotential of Alkyn-nCOF-cRGD has been demonstrated in vitro and in\nvivo models. It shows significantly improved drug uptake and targeted\ncell death in TNBC, highlighting the efficacy of receptor-mediated\nendocytosis and pH-controlled drug release. This strategy leverages\nthe unique properties of nCOFs with targeted drug delivery to achieve\nsignificant advances in personalized cancer therapy and set a new\nstandard for precision chemotherapeutic delivery.