Ultrasound-activated nanosonosensitizer for oxygen/sulfate dual-radical nanotherapy

An all-in-one therapy for cooperatively fighting cancer, infection and boosting wound repair is exceedingly demanded for patients with advanced superficial cancers or after surgical intervention to avoid multiple drug abuse and resultant adverse effects. Here, the ultrasound-activated nanosonosensitizer PHMP that integrated peroxymonosulfate (PMS) into the Pd-catalyzed hydrogenated mesoporous titanium dioxide (PHM) was dexterously designed for combined therapy of cancer and infected wound based on oxygen/sulfate dual-radical nanotherapy. Firstly, the PHM with single crystal structure and abundant oxygen deficiencies exhibited excellent ultrasound-excited reactive oxygen species (ROS) production for enhanced sonodynamic therapy (SDT) under the support of Pd nanozyme-mediated O₂ supply. Simultaneously, the physically targeted ultrasound irradiation effectively transformed PMS loaded in the hollow cavities into distinct sulfate radical (•SO₄^-) with longer half-life and stronger oxidation, which remarkably enhanced the therapeutic efficacy of PHM-mediated SDT for cancer and bacteria. In addition, by embedding PHMP into the hydrogel, the enrichment of PHMP in the focal site was guaranteed, and meanwhile a moist and ventilated environment was created to speed up wound repair. The study broadens the potential of •SO₄^- in the therapeutic fields and contributes a simple and appealing tactic for the comprehensive treatment of cancer, infection and wound repair.