Spatiotemporal controlled delivery of nanoparticles to injured vasculature
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 o...
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| 格式: | 文件 |
| 语言: | en_US |
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National Academy of Sciences
2011
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| 在线阅读: | http://hdl.handle.net/1721.1/60889 https://orcid.org/0000-0002-1381-8923 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1826195826484969472 |
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| author | Chan, Juliana Maria Zhang, Liangfang Tong, Rong Ghosh, Debadyuti Gao, Weiwei Liao, Grace V. Yuet, Kai P. Gray, David Rhee, June-Wha Cheng, Jianjun Golomb, Gershon Libby, Peter Langer, Robert Farokhzad, Omid C. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Chan, Juliana Maria Zhang, Liangfang Tong, Rong Ghosh, Debadyuti Gao, Weiwei Liao, Grace V. Yuet, Kai P. Gray, David Rhee, June-Wha Cheng, Jianjun Golomb, Gershon Libby, Peter Langer, Robert Farokhzad, Omid C. |
| author_sort | Chan, Juliana Maria |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:16:05Z |
| format | Article |
| id | mit-1721.1/60889 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:16:05Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/608892022-09-26T16:51:57Z Spatiotemporal controlled delivery of nanoparticles to injured vasculature Chan, Juliana Maria Zhang, Liangfang Tong, Rong Ghosh, Debadyuti Gao, Weiwei Liao, Grace V. Yuet, Kai P. Gray, David Rhee, June-Wha Cheng, Jianjun Golomb, Gershon Libby, Peter Langer, Robert Farokhzad, Omid C. 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 Langer, Robert Chan, Juliana Maria Ghosh, Debadyuti Liao, Grace V. Yuet, Kai P. Gray, David Langer, Robert 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. National Institutes of Health (U.S) (CA119349) National Institutes of Health (U.S) (EB003647) David H. Koch – Prostate Cancer Foundation 2011-02-04T12:59:40Z 2011-02-04T12:59:40Z 2010-02 2009-12 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/60889 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 20133865 https://orcid.org/0000-0002-1381-8923 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1073/pnas.0914585107 Proceedings of the National Academy of Sciences of the United States of America 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. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Chan, Juliana Maria Zhang, Liangfang Tong, Rong Ghosh, Debadyuti Gao, Weiwei Liao, Grace V. Yuet, Kai P. Gray, David Rhee, June-Wha Cheng, Jianjun Golomb, Gershon Libby, Peter Langer, Robert Farokhzad, Omid C. Spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| title | Spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| title_full | Spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| title_fullStr | Spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| title_full_unstemmed | Spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| title_short | Spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| title_sort | spatiotemporal controlled delivery of nanoparticles to injured vasculature |
| url | http://hdl.handle.net/1721.1/60889 https://orcid.org/0000-0002-1381-8923 https://orcid.org/0000-0003-4255-0492 |
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