Cited by 53Nanoparticle-Based Drug DeliveryRNA Interference and Gene DeliveryAdvancements in Transdermal Drug Delivery

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

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Luo, Jie, Molbay, Muge, Chen, Ying, Horvath, Izabela, Kadletz, Karoline, Kick, Benjamin, Zhao, Shan, Al-Maskari, Rami +32 more·2025·Nature Biotechnology

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.

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  • Several approaches for image analysis of LSFM datasets have been introduced in recent years, but these methods are typically limited to selected organs and do not provide integrated whole-body quantification of elongated structures.

    “Although several approaches for image analysis of light-sheet fluorescence microscopy (LSFM) datasets have been introduced in recent years6–10, these methods are typically limited to selected organs and do not provide integrated whole-body quantification of elongated structures.”
  • Tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking.

    “However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking.”
  • MouseMapper performs true 3D sliding-window inference on uncropped, multiterabyte datasets, rather than relying on 2D projections or precropped volumes.

    “In contrast to previous methods for whole-body analysis6,10,18, MouseMapper performs true 3D sliding-window inference on uncropped, multiterabyte datasets, rather than relying on 2D projections or precropped volumes, ensuring unbiased system-wide screening of anatomical changes for elongated structures.”

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Research works printed but not linked: 3

  1. [29]Al-Maskari, R., Paetzold, J. C., Horvath, I. & Erturk, A. On the pitfalls of deep image segmentation for lightsheet microscopy. In Medical Imaging with Deep Learning. MIDL 2022 Short Papers https://openreview.net/pdf?id=3Krfu84W-Wx (2022).
  2. [95]Luo, J. et al. Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning. PRIDE https://www.ebi.ac.uk/pride/archive/projects/PXD056871 (2024). PMC12700832 39809933
  3. [96]Luo, J. et al. Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning. GitHub https://github.com/erturklab/SCP-Nano (2024). PMC12700832 39809933

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Authors
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., Hoeher, 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., Arús, B. A., Bruns, O. T., Zeidler, R., Liesz, A., Protzer, U., Plesnila, N., Ussar, S., Hellal, F., Paetzold, J., Elsner, M., Dietz, H., & Erturk, A.
Affiliations
  • Helmholtz Munich (DE)
  • Technical University of Munich (DE)
  • University of Zurich (CH)
  • Munich Cluster for Systems Neurology (DE)
  • Institut für Schlaganfall- und Demenzforschung (DE)
  • Inserm (FR)
  • German Cancer Research Center (DE)
Corresponding author
Dietz, Hendrik
Venue
Nature Biotechnology
Published
2025-01-14
Volume
43
Issue
12
Pages
2009-2022
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W4406374671
Cited by
53
References
96
Citations by year
2026: 35 · 2025: 17
FWCI
10.90
Type
journal article
Language
en
Open access
Locations
  • Nature Biotechnology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection (cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (FOR2879, SFB 1052, EXC 2145, 457586042, EXC 2145SyNergy, 390857198, LI-2534/5-1)
  • Bundesministerium für Bildung und Forschung (01KX2121)
  • China Scholarship Council
  • NOMIS Stiftung
  • Stiftung zur Erforschung der Vaskulären Demenz
  • Helmholtz Artificial Intelligence Cooperation Unit
  • Helmholtz Zentrum München
  • H2020 European Research Council (802305)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Keywords
single-cell imaging, lipid nanoparticles, deep learning, targeted drug delivery, intramuscular injection, immune activation, liposomes, polyplexes, DNA origami, adeno-associated virus, whole-body imaging, mouse model
MeSH terms
Deep Learning, COVID-19, SARS-CoV-2, Dependovirus, Animals, Drug Carriers, Humans, Lipids, Liposomes, Tissue Distribution, Drug Delivery Systems, Mice, Nanoparticles, Single-Cell Analysis, Spike Glycoprotein, Coronavirus

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