Rationally Designed Benzobisthiadiazole‐Based Covalent Organic Framework for High‐Performance NIR‐II Fluorescence Imaging‐Guided Photodynamic Therapy

Abstract Although being applied as photosensitizers for photodynamic therapy, covalent organic frameworks (COFs) fail the precise fluorescence imaging in vivo and phototherapy in deep‐tissue, due to short excitation/emission wavelengths. Herein, this work proposes the first example of NIR‐II emissive and benzobisthiadiazole‐based COF‐980 . Comparing to its ligands, the structure of COF‐980 can more efficiently reducing the energy gap (Δ E S1‐T1 ) between the excited state and the triplet state to enhance photodynamic therapy efficiency. Importantly, COF‐980 demonstrates high photostability, good anti‐diffusion property, superior reactive oxygen species (ROS) generation efficiency, promising imaging ability, and ROS production in deep tissue (≈8 mm). Surprisingly, COF‐980 combined with laser irradiation could trigger larger amount of intracellular ROS to high efficiently induce cancer cell death. Notably, COF‐980 NPs precisely enable PDT guided by NIR‐II fluorescence imaging that effectively inhibit the 4T1 tumor growth with negligible adverse effects. This study provides a universal approach to developing long‐wavelength emissive COFs and exploits its applications for biomedicine.