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<p>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<sup>−1</sup>—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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月14日

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  • 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,
  • Alba Simats,
  • Vikramjeet Singh,
  • Igor Khalin,
  • Chenchen Pan,
  • Bernardo A. Arús,
  • Oliver T. Bruns,
  • Reinhard Zeidler,
  • Arthur Liesz,
  • Ulrike Protzer,
  • Nikolaus Plesnila,
  • Siegfried Ussar,
  • Farida Hellal,
  • Johannes Paetzold,
  • Markus Elsner,
  • Hendrik Dietz,
  • Ali Erturk

摘要

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.