Dual-Oxygenation/Dual-Fenton Synergistic Photothermal/Chemodynamic/Starvation Therapy for Tumor Treatment

Due to the complexity of tumor pathogenesis and the heterogeneity of the tumor microenvironment (TME), it is difficult to obtain satisfactory efficacy with a single therapy. In this study, a hyaluronic acid (HA)-modified ruthenium nanoaggregate (RuNA) and glucose oxidase (GOD)-loaded manganese dioxide (MnO2) nanoflowers (MRG@HA) have been prepared. RuNA and MnO2 nanoflowers can generate O2 in TME, alleviating tumor tissue hypoxia. RuNA is a good photothermal agent for high-temperature ablation of solid tumors under infrared laser irradiation. GOD consumes glucose in the presence of O2 and converts it into glucuronic acid and hydrogen peroxide, reducing tumor nutrient supply while promoting Fenton-like reactions of MnO2 nanoflowers and RuNA to produce cytotoxic hydroxyl radicals. MRG@HA can also actively target tumor cells through the affinity of HA and CD44 receptor to improve the antitumor effect. In vitro and in vivo studies have confirmed the synergistic effect of MRG@HA with tumor photothermal/chemodynamic/starvation therapy, showing its great potential for clinical application in tumor therapy.

Automated summary

In this study, a hyaluronic acid-modified ruthenium nanoaggregate and glucose oxidase-loaded manganese dioxide nanoflowers have been prepared. These nanomaterials can generate oxygen in the tumor microenvironment, alleviate tumor tissue hypoxia, and achieve high-temperature ablation of solid tumors. Additionally, they can consume glucose in the presence of oxygen, reduce tumor nutrient supply, and produce cytotoxic hydroxyl radicals, thereby enhancing the antitumor effect. The nanomaterials can also actively target tumor cells, improving the overall therapeutic effect.