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/Hf-Ir, for metabolic reprogramming and radiosensitization. BP/Hf-Ir disrupts oxidative phosphorylation and glycolysis, reducing energy production and alleviating hypoxia to enhance radiotherapy and anti-tumor immunity. BP/Hf-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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843481 | PMC |
| http://dx.doi.org/10.1039/d4sc08563a | DOI Listing |
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