A Direct Comparison of in Vitro and in Vivo Nucleic Acid Delivery Mediated by Hundreds of Nanoparticles Reveals a Weak Correlation

Mar 1, 2018Nano letters

Comparing Lab and Living Organism Delivery of Genetic Material by Hundreds of Nanoparticles Shows a Weak Link

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Abstract

A total of 281 lipid nanoparticles were analyzed for their ability to deliver DNA barcodes to cells in vitro and in vivo.

In vitro delivery of lipid nanoparticles did not predict their in vivo delivery to endothelial cells and macrophages.
Eighty-five lipid nanoparticles were evaluated for their targeting ability to eight splenic cell populations.
Cell types from myeloid progenitors were generally targeted by similar lipid nanoparticles compared to those from lymphoid progenitors.
Barcoded lipid nanoparticles provide insights into nanoparticle delivery mechanisms in living organisms.

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Endothelial cells and macrophages play active roles in disease and as a result are important targets for nucleic acid therapies. While thousands of chemically distinct lipid nanoparticles (LNPs) can be synthesized to deliver nucleic acids, studying more than a few LNPs in vivo is challenging. As a result, it is difficult to understand how nanoparticles target these cells in vivo. Using high throughput LNP barcoding, we quantified how well LNPs delivered DNA barcodes to endothelial cells and macrophages in vitro, as well as endothelial cells and macrophages isolated from the lung, heart, and bone marrow in vivo. We focused on two fundamental questions in drug delivery. First, does in vitro LNP delivery predict in vivo LNP delivery? By comparing how 281 LNPs delivered barcodes to endothelial cells and macrophages in vitro and in vivo, we found in vitro delivery did not predict in vivo delivery. Second, does LNP delivery change within the microenvironment of a tissue? We quantified how 85 LNPs delivered barcodes to eight splenic cell populations, and found that cell types derived from myeloid progenitors tended to be targeted by similar LNPs, relative to cell types derived from lymphoid progenitors. These data demonstrate that barcoded LNPs can elucidate fundamental questions about in vivo nanoparticle delivery.

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A Direct Comparison of in Vitro and in Vivo Nucleic Acid Delivery Mediated by Hundreds of Nanoparticles Reveals a Weak Correlation

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