A Heterojunction Structured WO2.9-WSe2 Nanoradiosensitizer Increases Local Tumor Ablation and Checkpoint Blockade Immunotherapy upon Low Radiation Dose.

Radiotherapy (RT) in practical use often suffers from off-target side effects and ineffectiveness against hypoxic tumor microenvironment (TME) as well as remote metastases. With regard to these problems, herein, we provide semiconductor heterojunction structured WO2.9-WSe2-PEG nanoparticles to realize a synergistic RT/photothermal therapy (PTT)/checkpoint blockade immunotherapy (CBT) for enhanced antitumor and antimetastatic effect. Based on the heterojunction structured nanoparticle with high Z element, the nanosystem could realize nonoxygen-dependent reactive oxygen species generation by catalyzing highly expressed H2O2 in TME upon X-ray irradiation, which could further induce immunogenic cell death. Meanwhile, this nanosystem could also induce hyperthermia upon near-infrared irradiation to enhance RT outcome. With the addition of anti-PD-L1 antibody-based CBT, our results give potent evidence that local RT/PTT upon mild temperature and low radiation dose could efficiently ablate local tumors, inhibit tumor metastasis as well as prevent tumor re-challenge. Our study provides not only one kind of radiosensitizer based on semiconductor nanoparticles but also a versatile nanoplatform for simultaneous triple-combined therapy (RT/PTT/CBT) for treating both local and metastasis tumors.