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Luo, J. ; Molbay, M. ; Chen, Y. ; Horvath, I. ; Kadletz, K. ; Kick, B.* ; Zhao, S. ; Al-Maskari, R. ; Singh, I. ; Ali, M. ; Bhatia, H.S. ; Minde, D.-P. ; Negwer, M. ; Höher, L. ; Calandra, G.M.* ; Groschup, B.* ; Su, J. ; Kimna, C. ; Rong, Z. ; Galensowske, N. ; Todorov, M.I. ; Jeridi, D. ; Ohn, T.-L. ; Roth, S.* ; Simats, A.* ; Singh, V.* ; Khalin, I.* ; Pan, C. ; Arus, B.A. ; Bruns, O.T. ; Zeidler, R. ; Liesz, A.* ; Protzer, U. ; Plesnila, N.* ; Ussar, S. ; Hellal, F. ; Paetzold, J.C. ; Elsner, M. ; Dietz, H.* ; Ertürk, A.

Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Nat. Biotechnol., DOI: 10.1038/s41587-024-02528-1 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Dna Origami; Protein Corona; Rna Delivery; Nanostructures; Receptor; Coreceptor; Interplay; Tissue
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Journal Nature Biotechnology
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Adipocytes & Metabolism (ADM)
Institute of Virology (VIRO)
Helmholtz Pioneer Campus (HPC)
Institute of Structural Biology (STB)
Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Research field(s) Enabling and Novel Technologies
Helmholtz Diabetes Center
Immune Response and Infection
Pioneer Campus
PSP Element(s) G-505800-001
G-507200-001
G-502700-003
G-510001-001
G-503010-001
G-502799-701
G-503800-001
Grants Vascular Dementia Research Foundation
China Scholarship Council
European Research Council
Turkish Ministry of Education
Helmholtz AI
BMBF (HIVacToGC)
Nomis Heart Atlas project grant (Nomis Foundation)
European Research Council Consolidator grant
German Federal Ministry of Education and Research (Bundesministerium fur Bildung und Forschung (BMBF)) within the NATON collaboration
DFG
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology
DOI 10.1038/s41587-024-02528-1
WOS ID 001395739100001
Scopus ID 85217244775
PubMed ID 39809933
Erfassungsdatum 2025-05-09
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