Macrophage Notch Ligand Delta-Like 4 Promotes Vein Graft Lesion Development

Koga, J.; Nakano, Toshiaki; Dahlman, James E.; Figueiredo, José Luiz; Zhang, Hengmin; Decano, Julius L.; Khan, Omar F.; Niida, Tomiharu; Iwata, Hiroshi; Aster, Jon C.; Yagita, Hideo; Anderson, Daniel G.; Ozaki, C. Keith; Aikawa, Masamichi

doi:10.1161/atvbaha.115.305516

Cited by 41 publications

(55 citation statements)

References 56 publications

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“…Nanoparticles were formulated in a microfluidic device by mixing DNA with lipomer, PEG, cholesterol, and a helper lipid, as previously described 5, 18, 19, 22–27, 42 . Nanoparticles were made with variable mole ratios of these constituents.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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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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Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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“…There is no doubt that recent technological advances in cellular and molecular biology, such as precise genetic editing and manipulation of human iPS-derived macrophages, 71,90 coupled with improved in vivo detection, 91 tracking and manipulation 92,93 of selective monocyte and macrophage subsets, will accelerate the translation of this increasing knowledge into effective therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Macrophages

Mallat

2017

ATVB

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“…4,6,34–36,58–62 Nanoparticles were made with variable mole ratios of these constituents. The nucleic acid ( e.g.…”

Section: Methods/experimentalmentioning

confidence: 99%

Analyzing 2000 in Vivo Drug Delivery Data Points Reveals Cholesterol Structure Impacts Nanoparticle Delivery

et al. 2018

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Lipid nanoparticles (LNPs) are formulated using unmodified cholesterol. However, cholesterol is naturally esterified and oxidized in vivo, and these cholesterol variants are differentially trafficked in vivo via lipoproteins including LDL and VLDL. We hypothesized that incorporating the same cholesterol variants into LNPs - which can be structurally similar to LDL and VLDL – would alter nanoparticle targeting in vivo. To test this hypothesis, we quantified how >100 LNPs made with 6 cholesterol variants delivered DNA barcodes to 18 cell types in wildtype, LDL R−/−, and VLDLR−/− mice that were both age-matched and female. By analyzing ~2,000 in vivo drug delivery data points, we found that LNPs formulated with esterified cholesterol delivered nucleic acids more efficiently than LNPs formulated with regular or oxidized cholesterol when compared across all tested cell types in the mouse. We also identified an LNP containing cholesteryl oleate that efficiently delivered siRNA and sgRNA to liver endothelial cells in vivo. Delivery was as - or more - efficient than the same LNP made with unmodified cholesterol. Moreover, delivery to liver endothelial cells was 3X more efficient than delivery to hepatocytes, distinguishing this oleate LNP from hepatocyte-targeting LNPs. RNA delivery can be improved by rationally selecting cholesterol variants, allowing optimization of nanoparticle targeting.

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Macrophage Notch Ligand Delta-Like 4 Promotes Vein Graft Lesion Development

Cited by 41 publications

References 56 publications

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

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

Macrophages

Analyzing 2000 in Vivo Drug Delivery Data Points Reveals Cholesterol Structure Impacts Nanoparticle Delivery

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