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

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-Paul; Negwer, Moritz; Hoeher, Luciano; Calandra, Gian Marco; Groschup, Bernhard; Su, Jinpeng; Kimna, Ceren ; Rong, Zhouyi ; Galensowske, Nikolas; Todorov, Mihail Ivilinov ; Jeridi, Denise; Ohn, Tzu-Lun; Roth, Stefan ; Simats, Alba; Singh, Vikramjeet ; Khalin, Igor ; Pan, Chenchen; Arús, Bernardo A. ; Bruns, Oliver T.; Zeidler, Reinhard ; Liesz, Arthur ; Protzer, Ulrike ; Plesnila, Nikolaus ; Ussar, Siegfried ; Hellal, Farida; Paetzold, Johannes; Elsner, Markus ; Dietz, Hendrik und Ertürk, Ali (2025): Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning. In: Nature Biotechnology [Forthcoming]

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1087-0156
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198