Modulation of the Tumor Immune Microenvironment by Bi2Te3-Au/Pd-Based Theranostic Nanocatalysts Enables Efficient Cancer Therapy

Nanozymes with multienzyme-mimicking activities have shown great potential in cancer therapy due to their ability to modulate the complex tumor microenvironment (TME). Herein, a second near-infrared (NIR-II) photothermal-nanocatalyst by decorating Bi2Te3 nanosheets with ultrasmall Au/Pd bimetallic nanoparticles (Bi2Te3-Au/Pd) to reverse the immunosuppressive TME is developed. The peroxidase (POD)-like and catalase (CAT)-like activities, and glutathione (GSH) consumption capacity of Au/Pd modulates the TME by disrupting the intracellular redox homeostasis and relieving hypoxia in the TME. Notably, the amplified oxidative stress induces the accumulation of lipid hydroperoxides (LPO) for enhanced ferroptosis. Moreover, upon NIR-II photoirradiation at 1064 nm, the localized heat generated by Bi2Te3 not only directly ablates the cancer cells but also enhances the Au/Pd-mediated catalysis-mediated cancer therapy. Furthermore, both in vitro and in vivo studies confirm that the Bi2Te3-Au/Pd nanocatalysts (BAP NCs) can effectively suppress tumor growth by inducing immunogenic cell death (ICD), and suppressing metastasis and recurrence by the synergistic treatment. Overall, this study provides a promising theranostic strategy for effective tumor inhibition.