Fluoro-Substitution of BODIPY Derivatives to Enhance Photothermal Conversion Efficiency for Near Infrared II Fluorescence Imaging and Immuno-photothermal Therapy

Immuno-photothermal therapy (IPTT) has emerged as a promising cancer treatment strategy. Developing photothermal agents (PTAs) with high performance is crucial in IPTT. Herein, a facile and efficient strategy is developed to enhance the photothermal conversion efficiency (PCE) of PTAs via multifluorination. Four BODIPY-based PTAs with different fluorine atoms, viz. <b>B-0F</b>, <b>B-1F</b>, <b>B-3F</b>, and <b>B-5F</b>, are developed. Increasing fluorination atoms on BODIPY not only red-shifts the absorption/emission wavelengths (<b>B-5F</b>: 786/940 nm) and improves the molar extinction coefficient but also facilitates the nonradiative transition for enhancing PCE. Hydrophobic <b>B-5F</b> was nanoassembled with PF-127, achieving water-dispersible nanoparticles (NPs) with a remarkable PCE of 67.4%. Under 808 nm laser irradiation, <b>B-5F</b> NPs demonstrate potent photothermal tumor ablation while inducing immunogenic cell death with the release of a damage-associated molecular pattern, resulting in significant tumor growth suppression. This work highlights a valuable approach to design efficient PTAs for IPTT of tumors.