Peroxidase-mimicking TA-VOx nanobranches for enhanced photothermal/chemodynamic therapy of glioma by inhibiting the expression of HSP60

Glioblastoma multiforme (GBM) is the most prevalent malignant brain tumor. It expresses high levels of heat shock protein (HSP60), which is associated with poor prognosis. Chemodynamic therapy (CDT) can be improved by photothermal therapy (PTT) and facilitate tumor eradication. Therefore, it is necessary to develop novel agents that synergize with the tumor killing effects of PTT/CDT by downregulating HSP60. Based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases and clinical cases, this study determined that HSP60 was upregulated and associated with reduced overall survival (OS) in GBM patients. Herein, TA-VOx nanobranches (TA-VOx NBs) were successfully synthesized by a one-step self-assembly procedure, which had excellent photothermal conversion characteristics and improved peroxidase-mimicking activity at elevated temperatures. Moreover, TA-VOx NBs can degrade to VO2+ in a slightly acidic tumor microenvironment. In vitro and in vivo studies showed that TA-VOx NBs synergized with PTT/CDT and improved glioma eradication under 808 nm irradiation due to the heat-induced ROS generation and the inhibition of HSP60. Furthermore, TA-VOx NBs were rapidly cleared by the kidney and showed good biosafety. Combined with the ease of fabrication, this is a promising nanomaterial that can be introduced for clinical translation in cancer therapy.