Tuning the Near-Infrared J-Aggregate of a Multicationic Photosensitizer through Molecular Coassembly for Symbiotic Photothermal Therapy and Chemotherapy

Abstract

Cationic photosensitizers (PSs) offer many intriguing advantages, in addition to generating heat or reactive oxygen species for cancer phototherapy. However, the preparation of cationic PSs with enhanced near-infrared (NIR) absorption remains a significant challenge. In this work, we have synthesized a PS TPBBT, which incorporates a strong electron-withdrawing unit, benzobisthiadiazole, and four terminal pyridinium groups. It self-assembles into a mixed H/J aggregated state with a maximal absorption peak at 620 nm but coassembles with negatively charged planar small molecules to form sole J-aggregates. Following this strategy, we coassemble TPBBT with rhein, a planar, anionic traditional Chinese medicine with an anticancer activity, which allows for a near 100 nm bathochromic shift of the maximal absorption of TPBBT and improves the photothermal conversion efficiency (PCE) of TPBBT from 6.4 to 60.4% under 808 nm laser irradiation. Additionally, coassembling with TPBBT significantly enhances the cellular uptake of rhein through the photothermal effect. The coassembly of TPBBT and rhein (TPBBTein) can completely eliminate 4T1 tumors on mouse models, validating that this facile strategy not only can tune the NIR J-aggregate of cationic PS through molecular coassembly but also promotes the efficient, symbiotic combination of photothermal therapy and chemotherapy.