Authors
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
Keywords
Nanocarriers, lipid nanoparticles, mRNA, targeted delivery, biodistribution, OTS mRNA
DOI
https://doi.org/10.1038/s41587-024-02528-1
Journal: Nature Biotechnology
PMID: 39809933
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.
