Near-infrared-responsive thia-hexaphyrin-based covalent organic frameworks for cancer phototherapy

Covalent organic frameworks (COF) have emerged as promising phototherapeutic platforms for tumor therapy, where the columnar π-arrayed metal-free photosensitizers serve as both a cooperative light-harvesting antenna and a semiconducting scaffold for efficient charge-carrier separation and transport. However, the phototherapeutic agents based on COFs are usually activated with ultraviolet and visible light, resulting in the limitation of deep-tissue phototherapy. Herein, we develop near-infrared-responsive COFs through elaborate design and synthesis of a thia-hexaphyrin building block, which feature well-aligned conjugation skeletons for the generation of reactive oxygen species (ROS) and photothermal effect upon 808 nm laser irradiation, outperforming conventional porphyrin-based COFs. This porous framework exhibits high phototherapeutic efficacy, leading to the tumor suppression for 4T1 tumors and CT26 tumors in female mouse model by inducing immunogenic cell death through phototherapy and triggering systemic anti-tumor immune responses.