HSP90 inhibitor-loaded hollow mesoporous nanoparticles for enhanced synergistic mild photothermal/chemotherapy in triple negative breast cancer

The combination of mild-temperature photothermal and chemotherapy represents a promising therapeutic strategy capable of maximizing anti-cancer efficacy while minimizing adverse reactions, particularly when integrated with multi-modal treatments. Nevertheless, the increase in heat shock protein (HSP) expression induced by mild hyperthermia may significantly influence the therapeutic efficacy. In this study, Isoliensinine (Iso) and the heat shock protein 90 (HSP90) inhibitor ganetespib were loaded into MPDA nanoparticles (NPs) to form GI-MPDA@BSA NPs, establishing a multi-modal therapeutic nanoplatform. The synthesized GI-MPDA@BSA NPs exhibit excellent photothermal conversion performance and favorable biocompatibility. Under 808 nm laser irradiation, the mild photothermal therapy (PTT) generated by MPDA facilitates the rapid release of drugs from BSA, resulting in an effective synergistic cytotoxic effect on cancer cells. Concurrently, the released ganetespib suppressed HSP90 expression, thereby potentiating the effects of mild photothermal/chemotherapy. In vitro and in vivo experimental results indicate that GI-MPDA@BSA exhibits low cytotoxicity while conspicuously inhibiting tumor growth under laser irradiation and eliciting an immune response. Furthermore, the application of two-dimensional ultrasound (2D US) and contrast-enhanced ultrasound (CEUS) to monitor post- tumor treatment changes elucidates the evolutionary process following combined mild-temperature photothermal/chemotherapy, presenting a novel strategy for the treatment and monitoring of triple negative breast cancer (TNBC) in clinical practice.