Metal–organic layer delivers 3-bromopyruvate to mitochondria for metabolic regulation and cancer radio-immunotherapy

Bian, Wangqing; Jiang, Xiaomin; Li, Jinhong; Tillman, Langston; Wang, Chaoyu; Zhen, Wenyao; Weichselbaum, Ralph R.; Fromme, Tobias; Lin, Wenbin

doi:10.6082/j5bc0-g0365

Published February 17, 2025 | Version v1

Journal article Open

Metal–organic layer delivers 3-bromopyruvate to mitochondria for metabolic regulation and cancer radio-immunotherapy

1. University of Chicago
2. Technical University of Munich

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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