Imbalanced redox homeostasis, involving either oxidative stress or reductive stress, can profoundly impact cellular functions, contributing to various diseases. While the implications of oxidative stress in the adverse effects of nanoparticles have been extensively studied, our comprehension of reductive stress within the context of nano-redox system interactions remains limited. Here we illuminate a domino effect initiated by the dehydrogenase-like activity of transition metal borides. Specifically, seven transition metal borides were identified to emulate the enzymatic activity of natural dehydrogenases, resulting in heightened levels of reductive constituents within critical biological redox pairs in cells. Mass cytometry analysis provides compelling evidence that reductive stress initiates an immunosuppressive environment within lung tissues, promoting the metastasis of breast cancer cells to the lungs. In summary, our study unveils the chemical basis of nano-induced reductive stress and establishes a mechanistic axis that interlinks dehydrogenase-like activity, reductive stress, immunosuppression and tumour metastasis.

Nanotechnology Centre Centre for Energy and Environmental Technologies VSB Technical University of Ostrava Ostrava Poruba Czech Republic

New Cornerstone Science Laboratory Laboratory of Theoretical and Computational Nanoscience National Center for Nanoscience and Technology University of Chinese Academy of Sciences Beijing China

School of Public Health Soochow University Suzhou China

Sino Danish College Sino Danish Center for Education and Research University of Chinese Academy of Sciences Beijing China

State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Suzhou Medical College Soochow University Suzhou China

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