Nanozyme-Incorporated Biodegradable Bismuth Mesoporous Radiosensitizer for Tumor Microenvironment-Modulated Hypoxic Tumor Thermoradiotherapy.

Solid tumors inevitably develop radioresistance due to low oxygen partial pressure in the tumor microenvironment. Despite numerous attempts, there are still few effective ways to avoid the hypoxia-induced poor radiotherapeutic effect. To overcome this problem, platinum (Pt) nanodots were fabricated into a mesoporous bismuth (Bi)-based nanomaterial to construct a biodegradable nanocomposite BiPt-folic acid-modified amphiphilic polyethylene glycol (PFA). BiPt-PFA could act as a radiosensitizer to enhance the absorption of X-rays at the tumor site and simultaneously trigger response behaviors related to the tumor microenvironment due to the enrichment of materials in the tumor area. During this process, the Bi-based component consumed glutathione via coordination, thus altering the oxidative stress balance, while Pt nanoparticles catalyzed the decomposition of hydrogen peroxide to generate oxygen, thereby relieving tumor hypoxia. Both Pt and Bi thus co-modulated the tumor microenvironment to improve the radiotherapeutic effect. In addition, Pt dots in BiPt-PFA had strong near-infrared absorption ability and created an intensive photothermal therapeutic effect. Modulation of the tumor microenvironment could thus improve the therapeutic effect in hypoxic tumors by a combination of photothermal therapy and enhanced radiotherapy. BiPt-PFA, as a biodegradable nanocomposite, may thus modulate the tumor microenvironment to enhance the hypoxic tumor therapeutic effect by thermoradiotherapy.