体内
体外
核酸
细胞生物学
药物输送
祖细胞
化学
生物
细胞
干细胞
生物化学
遗传学
有机化学
作者
Kalina Paunovska,Cory D. Sago,Christopher M. Monaco,William Henry Hudson,Lena Gamboa,Tobi G. Rudoltz,Sujay Kalathoor,Daryll Vanover,Philip J. Santangelo,Rafi Ahmed,Anton V. Bryksin,James E. Dahlman
出处
期刊:Nano Letters
[American Chemical Society]
日期:2018-02-28
卷期号:18 (3): 2148-2157
被引量:141
标识
DOI:10.1021/acs.nanolett.8b00432
摘要
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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