Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning
Creators
- Luo, Jie
- Molbay, Muge
- Chen, Ying
- Horvath, Izabela
- Kadletz, Karoline
- Kick, Benjamin
- Zhao, Shan
- Al-Maskari, Rami
- Singh, Inderjeet
- Ali, Mayar
- Bhatia, Harsharan Singh
- Minde, David-Paul1
- Negwer, Moritz
- Hoeher, Luciano1
- Calandra, Gian Marco
- Groschup, Bernhard
- Su, Jinpeng
- Kimna, Ceren
- Rong, Zhouyi
- Galensowske, Nikolas1
- 1. Helmholtz Ctr Munich, Inst Intelligent Biotechnol iBIO, Neuherberg, Germany
Description
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.
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