Microwave Triggered NO/O 2 Dual Gas Release Nano Synergistic System for Overcoming Tumor Thermotherapy Resistance and Activating Immunotherapy

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Abstract
Microwave thermotherapy, as an effective physical therapy for solid tumors, often leads to treatment resistance due to limitations such as hypoxia and abnormal blood vessels, resulting in tumor residue, metastasis, and recurrence. This study constructed a microwave‐responsive multifunctional nanocomposite (CCGM NCs). Using cobalt‐gallium (Co‐Ga) nanosheets as carriers, NO donor S‐nitrosocysteine is loaded, and temperature‐controlled material L‐menthol is coated to form a synergistic delivery system with thermal switch characteristics. Under microwave radiation, the material simultaneously achieves three functions: acting as a microwave sensitizer to generate local thermotherapy. Catalytic generation of O 2 from hydrogen peroxide decomposition within the tumor and release of NO through microwave irradiation. The synergistic effect of O 2 and NO inside the tumor not only alleviates hypoxia and improves vascular function, but also generates peroxynitrite anions, which work together with thermotherapy and reactive nitrogen species to enhance tumor killing. This system can effectively induce immunogenic cell death and initiate systemic anti‐tumor immune responses. Through the validation of bilateral tumor models and lung metastasis models, this strategy can efficiently ablate in situ tumors while stimulating significant distal tumor suppression and immune memory effects, effectively inhibiting tumor metastasis and recurrence.
Funding Information
  • National Natural Science Foundation of China (62405333)
  • National Natural Science Foundation of China (82271948)
  • Natural Science Foundation of Beijing Municipality (L248042)

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