Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning
- PMID: 39809933
- DOI: 10.1038/s41587-024-02528-1
Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning
Abstract
Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.0005 mg kg-1-far below the detection limits of conventional whole body imaging techniques. We demonstrate that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to proteome changes, suggesting immune activation and blood vessel damage. SCP-Nano generalizes to various types of nanocarriers, including liposomes, polyplexes, DNA origami and adeno-associated viruses (AAVs), revealing that an AAV2 variant transduces adipocytes throughout the body. SCP-Nano enables comprehensive three-dimensional mapping of nanocarrier distribution throughout mouse bodies with high sensitivity and should accelerate the development of precise and safe nanocarrier-based therapeutics.
© 2025. The Author(s).
Conflict of interest statement
Competing interests: A.E., J.L., K.K., I.H. and R.A.-M. have filed for intellectual property on AI-based technologies described herein. A.E. is a co-founder of Deep Piction. The other authors declare no competing interests.
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