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
Highlights
Bioluminescence imaging (ventral) 6 h after intravenous injection of 0.5 mg kg−1 luciferase mRNA-carrying LNPs in C57BL/6 mice.
Source: Adapted from Article under the CC BY 4.0 license. Visual design and formatting modified by RIBOPRO.
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.
