Dual-Oxygenation/Dual-Fenton\nSynergistic Photothermal/Chemodynamic/Starvation\nTherapy for Tumor Treatment

Abstract

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