Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011.

Bibliographic Details
Main Author: Wong, Cliff R. (Cliff Richard)
Other Authors: Moungi Bawendi.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2011
Subjects:
Online Access:http://hdl.handle.net/1721.1/63062
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author Wong, Cliff R. (Cliff Richard)
author2 Moungi Bawendi.
author_facet Moungi Bawendi.
Wong, Cliff R. (Cliff Richard)
author_sort Wong, Cliff R. (Cliff Richard)
collection MIT
description Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011.
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spelling mit-1721.1/630622022-01-13T07:54:21Z Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth Wong, Cliff R. (Cliff Richard) Moungi Bawendi. Massachusetts Institute of Technology. Dept. of Chemistry. Massachusetts Institute of Technology. Department of Chemistry Chemistry. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2011. Cataloged from PDF version of thesis. Includes bibliographical references. Assembly of functional nanocomponents offers promising applications in drug delivery to solid tumors and bottom-up synthesis and integration of nanodevices. This thesis presents a novel multistage nanoparticle delivery system consisting of an assembly of nanoparticles that can change its size to facilitate transport into solid tumors. Current FDA-approved nanotherapeutics, which function based on the enhanced permeation and retention (EPR) effect, suffer from poor penetration into the extravascular regions of the tumor due to the dense collagen matrix, resulting in heterogeneous therapeutic effects and likely contributing to tumor regression and development of resistance. We propose a multistage nanoparticle system that "shrinks" when it extravasates into the tumor and is exposed to the tumor microenvironment, allowing enhanced penetration into the tumor parenchyma. This "shrinkage" is preferentially triggered in the tumor through cleavage by MMPs, proteases highly expressed in the tumor microenvironment. A multistage nanoparticle system allows us to engineer the size and surface properties of each stage independently for preferential transvascular transport into tumors and high diffusion in the tumor's interstitial space. To our knowledge, this work is the first demonstration of a size-changing nanoparticle delivery system in vivo. Multistage nanoparticle delivery systems provide a promising approach to improving the delivery of anticancer agents into solid tumors and as a result the enhancement of the drug's therapeutic efficacy. Another area that necessitates the controlled assembly of nanocomponents is in the integration of nanodevices and nanocircuitry. We have developed a method of combining the synthesis and assembly of semiconducting nanowires in a single step using electrically controlled catalytic nanowire growth. Our results demonstrate electric field-modulated nanowire growth that can be used as a simple and inexpensive method for fabricating and integrating nanoscale devices. by Cliff R. Wong. Ph.D. 2011-05-23T18:11:19Z 2011-05-23T18:11:19Z 2011 2011 Thesis http://hdl.handle.net/1721.1/63062 724758971 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 137 p. application/pdf Massachusetts Institute of Technology
spellingShingle Chemistry.
Wong, Cliff R. (Cliff Richard)
Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
title Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
title_full Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
title_fullStr Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
title_full_unstemmed Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
title_short Multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
title_sort multistage nanoparticle delivery system for deep penetration into solid tumor and electrically controlled catalytic nanowire growth
topic Chemistry.
url http://hdl.handle.net/1721.1/63062
work_keys_str_mv AT wongcliffrcliffrichard multistagenanoparticledeliverysystemfordeeppenetrationintosolidtumorandelectricallycontrolledcatalyticnanowiregrowth