A mitochondria-targeted biocompatible photothermal nanoscale hydrogen-organic framework for effective multimodal-imaging guided breast cancer therapy

Organic small-molecule photothermal agents (smPTAs) have been extensively studied for biomedical applications due to their good biocompatibility comparing with inorganic materials. However, most smPTAs suffer from water insolubility, even organic solvents insolubility, poor bio- and photo-stability, and short blood half-life. Herein, a new type of salinized 4,4′-(benzo[1,2-d:4,5-d']bis(thiazole)-2,6-diyl)dibenzoic acid (BBTDB-Na) smPTA is synthesized via a cyano group of 2-cyano-benzothiazole (CBT)-1,2-aminothiol group of cysteine (Cys) click condensation reaction, and photothermal nanoscale hydrogen-bonded organic frameworks (BT-nHOFs) is further constructed through a facile self-assembly strategy. The prepared BT-nHOFs exhibit a fusiform shape and bisthiazole structure, resulting in good cellular uptake and mitochondrial targeting effects. The well-organized structure of HOFs enables excellent photostability and high photothermal efficiency (51.4 %). Under 808 nm laser irradiation, the BT-nHOFs show favorable photothermal effects on breast cancer cells in vitro and in vivo, indicating that BT-nHOFs can act as a biocompatible PTA candidate for clinical applications. Besides, the fluorescence features, photoacoustic ability, cargo loading capacity of BT-nHOFs furnish multimodal imaging-guided precise photothermal therapy. In summary, this work paves a new way for the development of photothermal HOFs by salinizing insoluble smPTA and demonstrates their great potential for clinical application in phototheranostics.