德国慕尼黑大学Ali Erturk等研究人员合作使用深度学习对整个小鼠体内纳米载体进行单细胞分辨率成像。2025年1月14日，《自然—生物技术》杂志在线发表了这项成果。

研究人员提出了单细胞精度纳米载体识别（SCP-Nano），这是一种集成的实验与深度学习管道，可以在单细胞分辨率下全面量化纳米载体在整个小鼠体内的靶向分布。SCP-Nano揭示了脂质纳米颗粒（LNP）在不同注射途径下的组织分布模式，剂量低至0.0005 mg/kg，远低于传统全身成像技术的检测限。

研究人员展示了通过肌肉注射携带SARS-CoV-2刺突蛋白mRNA的LNP可以到达心脏组织，引发蛋白质组的变化，并提示免疫激活和血管损伤。

SCP-Nano还适用于各种类型的纳米载体，包括脂质体、多聚体、DNA折纸和腺病毒相关病毒（AAV），并揭示AAV2变种能够在全身转导脂肪细胞。SCP-Nano实现了高灵敏度的纳米载体在小鼠体内分布的全面三维映射，预计将加速精确且安全的纳米载体基础治疗的开发。

研究人员表示，高效准确的纳米载体开发用于靶向药物递送，但由于缺乏能够在整个有机体内分析其细胞级生物分布的方法，导致这一进程受到阻碍。

附：英文原文

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

Author: 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, Ars, Bernardo A., Bruns, Oliver T., Zeidler, Reinhard, Liesz, Arthur, Protzer, Ulrike, Plesnila, Nikolaus, Ussar, Siegfried, Hellal, Farida, Paetzold, Johannes, Elsner, Markus, Dietz, Hendrik, Erturk, Ali

Issue&Volume: 2025-01-14

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 0.0005mgkg1—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.

DOI: 10.1038/s41587-024-02528-1

Source: https://www.nature.com/articles/s41587-024-02528-1