Spatiotemporal controlled delivery of nanoparticles to injured vasculature
Name
Chan-2010-Spatiotemporal contr.pdf
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802.88 KB
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Checksum (MD5)
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Author(s)
Chan, Juliana Maria
Zhang, Liangfang
Tong, Rong
Ghosh, Debadyuti
Gao, Weiwei
Liao, Grace V.
Yuet, Kai P.
Gray, David
Rhee, June-Wha
Cheng, Jianjun
Date Issued
February 2010
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences
Citation
Chan, Juliana M. et al. “Spatiotemporal controlled delivery of nanoparticles to injured vasculature.” Proceedings of the National Academy of Sciences 107.5 (2010): 2213 -2218. Copyright ©2010 by the National Academy of Sciences
Version
Final published version
Abstract
There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (i) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (ii) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50–150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.0914585107
