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Overtreatment as a crucial modern medicine issue needs to be urgently addressed. Theranostic agents supply a unique platform and integrate multiple diagnosis and therapies to deal with this issue. In this study, a core-shell MnS@BiS nanostructure was fabricated via two step reactions for tri-modal imaging guided thermo-radio synergistic therapy. The mass ratio between the core and shell of the constructed MnS@BiS can be precisely controlled via cation exchange reaction. After surface PEGylation, MnS@BiS-PEG nanoparticles exhibited excellent aqueous medium dispersibility for bioapplications. Based on the r and r relaxivity obtained from the MnS core and the strong near-infrared absorption and X-ray attenuation abilities of the BiS shell, the intratumoral injected MnS@BiS-PEG can realize in vivo magnetic resonance, computer tomography, and photoacoustic tumor imaging under a single injection dose. Hyperthermia significantly boosts the efficacy of radiation therapy, showing synergistic tumor treatment efficacy. No obvious toxicity is monitored for the treated mice. Our study not only provides a new way to precisely construct the core-shell nanocomposite, but also presents a unique theranostic platform and unifies the solutions for the challenges related with high injection dose and overtreatment.

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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.

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