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 (MnO) nanoflowers (MRG@HA) have been prepared. RuNA and MnO nanoflowers can generate O 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 O and converts it into glucuronic acid and hydrogen peroxide, reducing tumor nutrient supply while promoting Fenton-like reactions of MnO 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. and 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.