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Chemico-physical and pharmacologic factors that influence delivery of IONPs to tumors in rodent breast cancer models / by Jennifer Tate.

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Author	Tate, Jennifer.
Title	Chemico-physical and pharmacologic factors that influence delivery of IONPs to tumors in rodent breast cancer models / by Jennifer Tate.
Date	2013
Abstract	Nanoparticles have made significant advances in recent years in the realm of cancer therapy. These nanoparticles typically range in size from 10-250nm in diameter, allowing for differential systemic-based biodistribution. The enhanced permeability and retention (EPR) effect favors nanoparticle tumor accumulation due to unorganized tumor vasculature and poor lymphatic drainage, however is extremely variable between tumors. Leveraging nanoparticle design, therefore, is crucial to successful systemically-delivered tumor accumulation. This research focuses on characterizing key design parameters for iron oxide nanoparticles (IONP). When exposed to an external alternating magnetic field (AMF), IONPs can activate to deposit localized energy in the form of heat. This technology has been established clinically with directly-injected IONP, however intravenous administration faces the challenge of accumulating sufficient IONP at the target site to achieve therapeutic effect. IONP design, including content, size, surface coating and targeting functionalization, will critically influence tumor uptake, biodistribution and subsequent therapeutic effect. In the work presented here, IONPs of various sizes and surface functionalizations, including antibody fragment-targeted and PEG-ylated, were assessed for cell uptake kinetics in four different cell lines as well as intravenously administered in murine and human breast cancer mouse models to determine biodistribution. Cell uptake kinetics and in vivo biodistribution were characterized with ferrozine assay, inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM). Coadministration of a novel vasculature modifying agent, iRGD peptide, was also examined in vivo for its potential to increase tumor uptake. Results indicated that 20nm trastuzumab Fab (tFab)-targeted IONPs resulted in a 3-fold increase in tumor iron content, as compared to larger targeted IONPs. tFab-targeted 20nm IONPs increased tumor iron content 2-fold as compared to non-tar
Description	xv, 133, 124 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	P. Jack Hoopes, Karl E. Griswold, Lionel D, Lewis, Brian W. Pogue, Kevin D. Isett
College	Thayer School of Engineering.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1008

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Chemico-physical and pharmacologic factors that influence delivery of IONPs to tumors in rodent breast cancer models / by Jennifer Tate.

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