Hyaluronic acid-based dual-responsive nanomicelles mediated mutually synergistic photothermal and molecular targeting therapies

Precise clinical treatment of triple-negative breast cancer (TNBC) is an obstacle in clinic. Nanotechnology-assisted photothermal therapy (PTT) is a superior treatment modality for TNBC in terms of precision. However, thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT. AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study, showing satisfactory antitumour activity through molecularly targeted therapy (MTT). Whereas, it has poor solubility. Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds, forming an amphipathic copolymer that could self-assembled into nanomicelles, followed by encapsulating Cypate and AT13387. These nanomicelles exhibited great features, including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs, increasing the solubility of Cypate and AT13387, showing a pH/redox dual response that contributes to drug release, and having the ability of active targeting. Thus, the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.