Thermo-responsive gold nanorod vesicles for combined NIR-II photothermal therapy and chemotherapy of solid tumors

Photothermal therapy (PTT) is a promising treatment strategy for malignant tumors. Photothermal agents which can achieve efficient photothermal conversion in the NIR-II region plays crucial roles in this remedy. Here, we report one type of thermo-responsive gold nanorod vesicles USGRV-17-AAG for combined NIR-II photothermal therapy and chemotherapy of solid tumors. The nanovesicles are formed by self-assembly of gold nanorods modified with amphiphilic polymers (PEG₄₅-b-PS₄₅₀) and UCST-type polymers (P(AAm-co-AN)), and are loaded with the heat shock protein inhibitor 17-AAG. Upon 1064 nm laser irradiation, USGRV-17-AAG exhibits a high photothermal conversion efficiency (65.1 %) and thus can achieve temperature responsive release of tanespimycin (17-AAG), an inhibitor of HSP90. The combination of NIR-II photothermal therapy and chemotherapy can effectively eliminate tumor cells and inhibit the expression of HSP90. Intravenous injection of USGRV-17-AAG followed by 1064 nm laser irradiation revealed efficacious tumor ablation of tumor-bearing mice, with a tumor growth inhibition rate of 98.86 %. Therefore, USGRV-17-AAG can produce efficient anti-tumor effects and provides an alternative approach to the treatment of malignant tumors. STATEMENT OF SIGNIFICANCE: Photothermal conversion agents (PTAs) based on the near-infrared II (NIR-II) window are currently attracting significant attention for their promising development and diverse applications. In this study, thermosensitive drug-loaded nanovesicles, USGRV-17-AAG, were designed to enable NIR-II photothermal therapy in combination with chemotherapy. These nanovesicles were loaded with the heat shock protein 90 (HSP90) inhibitor 17-AAG, which effectively inhibits HSP90 expression and enhances the therapeutic efficacy of photothermal treatment. Additionally, USGRV-17-AAG exhibited efficient photothermal conversion (65.1 %) under 1064 nm laser irradiation and enabled temperature-responsive drug release through the action of surface-modified upper critical solution temperature (UCST) polymers. This nanocarrier, with enhanced NIR-II photothermal therapy, might offer a promising solution for anti-tumor treatment.