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

ABSTRACT: Efficient and accurate nanocarrier development for targeted drug delivery is hindered by the inability to analyze cell-level biodistribution across intact whole organisms. We introduce SCP-Nano (Single Cell Precision Nanocarrier Identification), a deep learning pipeline designed to quantify the targeting of millions of cells by nanocarriers in whole-mouse bodies imaged at cellular resolution. SCP-Nano revealed the tissue distribution patterns of lipid nanoparticles (LNPs) following different injection routes at doses as low as 0.0005 mg/kg—far below the detection limits of conventional whole-body imaging techniques. Notably, we demonstrated that LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to changes in the heart's protein composition that suggest immune activation and possible blood vessel damage. Additionally, we showed that SCP-Nano can analyze various types of nanocarriers, including liposomes, polyplexes, DNA origami, and adeno-associated viruses (AAVs). SCP-Nano's high sensitivity enables accurate 3D mapping of nanocarrier distribution throughout mouse bodies, even detecting very low levels in unexpected tissues. SCP-Nano is poised to accelerate the development of precise and safe nanocarrier-based therapeutics.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

SUBMITTER: Ali Erturk  

LAB HEAD: Prof. Ali

PROVIDER: PXD056871 | Pride | 2024-12-06

REPOSITORIES: Pride