Preclinical study demonstrates marked tumor suppression and metastasis inhibition in mouse models, highlighting the therapeutic potential of mitochondrial metabolic disruption for radio-immunotherapy.
Abnormal cancer metabolism causes hypoxia and immunosuppression, limiting the anti-tumor efficacy of radiotherapy. Herein, we report a positively charged, mitochondria-targeted nanoscale metal-organic layer conjugated with 3-bromopyruvate (BP), BP/Hf₁₂-Ir, for metabolic reprogramming and radiosensitization. BP/Hf₁₂-Ir disrupts oxidative phosphorylation and glycolysis, reducing energy production and alleviating hypoxia to enhance radiotherapy and anti-tumor immunity. BP/Hf₁₂-Ir in combination with X-ray irradiation inhibits tumor growth by 95% and prevents lung metastasis in mouse models. When further combined with immune checkpoint blockade, this treatment induces robust anti-tumor immunity, achieving 98% tumor growth inhibition.
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Bian et al. (2025) studied this question.
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