The biotransformation of nanoparticles plays a crucial role in determining their biological fate and responses. Although a few engineering strategies (e.g., surface functionalization and shape control) have been employed to regulate the fate of nanoparticles, the genetic control of nanoparticle biotransformation remains an unexplored avenue. Herein, we utilized a CRISPR-based genome-scale knockout approach to identify genes involved in the biotransformation of rare earth oxide (REO) nanoparticles. We found that the biotransformation of REOs in lysosomes could be genetically controlled via SMPD1. Specifically, suppression of SMPD1 inhibited the transformation of La2O3 into sea urchin-shaped structures, thereby protecting against lysosomal damage, proinflammatory cytokine release, pyroptosis and RE-induced pneumoconiosis. Overall, our study provides insight into how to control the biological fate of nanomaterials.

Institute of Environmental Systems Biology College of Environmental Science and Engineering Dalian Maritime University Dalian Liaoning P R China

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

School of Ecology and Environmental Science Yunnan University and Yunnan Key Laboratory for Plateau Mountain Ecology and Restoration of Degraded Environments Kunming Yunnan China

State Key Laboratory of Pollution Control and Resource Reuse School of the Environment Nanjing University Nanjing P R China

State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Soochow Medical College Soochow University Suzhou P R China

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