2025-01-14 ミュンヘン大学(LMU)
<関連情報>
- https://www.lmu.de/en/newsroom/news-overview/news/tracking-delivery-new-technology-for-nanocarriers.html
- https://www.nature.com/articles/s41587-024-02528-1
ディープラーニングでマウスの体全体を単一細胞解像度でナノキャリアイメージング Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning
Jie Luo,Muge Molbay,Ying Chen,Izabela Horvath,Karoline Kadletz,Benjamin Kick,Shan Zhao,Rami Al-Maskari,Inderjeet Singh,Mayar Ali,Harsharan Singh Bhatia,David-Paul Minde,Moritz Negwer,Luciano Hoeher,Gian Marco Calandra,Bernhard Groschup,Jinpeng Su,Ceren Kimna,Zhouyi Rong,Nikolas Galensowske,Mihail Ivilinov Todorov,Denise Jeridi,Tzu-Lun Ohn,Stefan Roth,… Ali Erturk
Nature Biotechnology Published:14 January 2025
DOI:https://doi.org/10.1038/s41587-024-02528-1
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.
