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Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning
Jie Luo1,2,3,4, Muge Molbay1,2,5,6, Ying Chen1,2,3,5,7
1Institute for Intelligent Biotechnologies (iBIO), Helmholtz Center Munich, Neuherberg, Germany.
Nature Biotechnology
|January 14, 2025
Summary
A new method, Single Cell Precision Nanocarrier Identification (SCP-Nano), precisely maps nanocarrier biodistribution in mice at the single-cell level. This technology enhances nanocarrier development for targeted drug delivery and safety assessments.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Accurate analysis of nanocarrier cell-level biodistribution in whole organisms is crucial for targeted drug delivery.
- Current whole-body imaging techniques lack the sensitivity to detect low-dose nanocarrier distribution.
Purpose of the Study:
- To develop an integrated experimental and deep learning pipeline, SCP-Nano, for high-resolution, whole-body nanocarrier biodistribution analysis.
- To enable sensitive quantification of nanocarrier targeting at the single-cell level.
Main Methods:
- Developed Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline.
- Applied SCP-Nano to analyze lipid nanoparticle (LNP) distribution after different injection routes in mice.
- Validated SCP-Nano's generalizability across various nanocarrier types, including liposomes, polyplexes, DNA origami, and adeno-associated viruses (AAVs).
Main Results:
- SCP-Nano quantified nanocarrier tissue distribution at single-cell resolution, even at doses below 0.0005 mg/kg.
- Demonstrated that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reached heart tissue, causing proteome changes indicative of immune activation and potential blood vessel damage.
- Revealed that an AAV2 variant transduced adipocytes throughout the body.
Conclusions:
- SCP-Nano provides sensitive, comprehensive 3D mapping of nanocarrier distribution in mouse bodies.
- This technology accelerates the development of precise and safe nanocarrier-based therapeutics.
- SCP-Nano facilitates detailed analysis of nanocarrier interactions with tissues and cellular targets.
