Bimetallic PdPt-based nanocatalysts for Photothermal-Augmented tumor starvation and sonodynamic therapy in NIR-II biowindow assisted by an oxygen Self-Supply strategy

Abstract

Tumor starvation by depleting intratumoral glucose has been validated as a promising therapeutic strategy to combat cancer. However, inadequate oxygenation in hypoxic tumorous tissue significantly compromises the treatment efficacy. Herein, PdPt bimetallic nanocatalyst conjugated with glucose oxidase (GOx) and sonosensitizer IR780 is developed for photothermal-augmented tumor starvation and sonodynamic therapy (SDT) in near-infrared (NIR)-II biowindow, assisted by an oxygen self-supply strategy. As a catalase-mimicking nanozyme, PdPt@GOx/IR780 (PGI) can facilitate the alleviation of tumor hypoxia through catalyzing H2O2 decomposition into O2. Furthermore, GOx-mediated intratumoral glucose consumption may block the essential energy and nutrient supply to achieve tumor starvation. The resultant H2O2 production enables a continuous supply of local O2, which subsequently aggravates glucose depletion. Meanwhile, the hypoxia alleviation also promotes the production of 1O2 for a more efficacious SDT with the aid of sonosensitizer IR780. In another aspect, hyperthermia generation by PGI under NIR-II laser irradiation leads to the thermal ablation of tumor cells, which effectively incorporates with tumor starvation and SDT for a complete tumor eradication. More importantly, the combination therapy can trigger strong immunogenic cell death (ICD), which favors the overcoming of immune suppression and the enhancement of antitumor immunity. The admirable tumor suppression effect by PGI is demonstrated on tumor-bearing mice with minimal adverse effect. Taken together, this paradigm provides a useful strategy for PdPt functionalization in the pursuit of effective tumor therapy with high clinical relevance.