Photothermally Enhanced Dual Enzyme-mimic Activity of Gold-Palladium Hybrid Nanozyme for Cancer Therapy

Based on characteristics of the tumor microenvironment (TME), including acidity, hypoxia, inflammation and hydrogen peroxide overload, combined with emerging nanotechnologies, designing nanoplatforms with TME specificity/responsiveness for tumor treatment is a promising nanotherapeutic strategy. In this work, a multifunctional gold-palladium bimetallic cascade nanozyme was constructed for effective photothermal-enhanced cascade catalyzed synergistic therapy of tumors. The dumbbell-like Au-Pd bimetallic nanomaterial (Au NRs-Pd@HA) was obtained by reducing palladium on gold nanorods with ascorbic acid (AA) and further modified with hyaluronic acid (HA). The introduction of HA brings biocompatibility and targeting properties. The zebrafish embryos model showed that Au NRs-Pd@HA had good biocompatibility and low biotoxicity. Au NRs-Pd@HA can induce catalytic conversion of glucose to generate H2O2 efficiently, and subsequently undergo cascade reaction to produce abundant & BULL;OH radicals, exhibiting peroxidase-like (POD-like) and glucose oxidase-like (GOD-like) capabilities. The generated & BULL;OH was a key factor for tumor ablation. Meanwhile, Au NRs-Pd@HA exhibits good photothermal performance under 808 nm irradiation, in favor of photothermal therapy (PTT). Especially, the POD-like and GOD-like activities were significantly enhanced due to the photothermal effect. The synergistic PTT and photothermal-enhanced nanozymes with cascade catalytic effect enabled efficient and safe cancer therapy.