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Multimodal nanoparticle-based platforms for cancer therapy
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Multimodal nanoparticle-based platforms for cancer therapy
Identifier
ETD_2934
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056449
Language
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(authority = ISO639-2);
(type = code)
eng
Genre
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theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Cancer--Treatment
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Nanoscience--Methodology
Abstract
(type = abstract)
Nanoscience has attracted attention as a fast burgeoning field with promising methodologies for cancer diagnosis and therapy. We designed target-specific nanoparticle -based platforms to induce the apoptosis of human brain cancer cells and to show their capability for in vivo theragnostics which combines therapy and diagnosis. Quantum Dot (QD)-based system was demonstrated to deliver siRNA and monitor its uptake using extremely bright fluorescence of QDs. siRNA-QDs against GFP not only showed increased efficiency of transfection, but also synchronized QDs’ color and their localization. As a model study, glioblastoma multiforme (GBM) was chosen because of high malignancy and invasiveness resulting in short mean survival rate. Multiplexing with integrin-targeting RGD and TAT peptide enabled siRNA-QDs to be delivered specifically to U87 cells, a GBM cell line with highly expressed integrin. As a chemotheragnostic agent, siRNA-QDs were transfected into GBM cells that overexpress epidemic growth factor receptor variant III (EGFRvIII). Efficiently delivered siRNA-QDs against EGFRvIII led to abnormal cell morphology and decreased cell population. These were caused by successful knockdown of EGFRvIII gene and resulting silencing of the PI3K/AKT signaling pathway, which plays an important role in cancer proliferation and apoptosis. In spite of high potential of siRNA-QD system, cytotoxicity and skin depth issues lead to the development of a magnetic nanoparticle (MNP)-based theragnostic system for in vivo application. Graphite-coated FeCo MNPs (FeCo/C) exhibited superparamagnetic properties with high crystallinity and magnetization. In addition, Raman imaging is made possible by graphite shell designed for protection of FeCo core from decomposition and oxidation. Compared to conventional iron oxide MNPs, FeCo/C showed much higher T2-weighted magnetic resonance contrast. Dextrans were also developed to stabilize FeCo/C in physiological condition as well as to conjugate therapeutic or targeting molecules such as siRNA, antibody, and cyclic RGD. High magnetization of FeCo/C allowed for target-specific hyperthermia against U87 cells by local heating under AC magnetic field. Additionally, siRNA-FeCo/C against EGFRvIII followed by hyperthermia synergistically induced significant cell death of U87-EGFRvIII, which proved that the target-specific siRNA-FeCo/C system is a promising candidate for in vivo theragnostic agent.
PhysicalDescription
Form
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electronic resource
Extent
xv, 142 p. : ill.
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application/pdf
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text/xml
Note
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Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Jongjin Jung
Name
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Jung
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Jongjin
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author
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Jongjin Jung
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Lee
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Ki-Bum
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chair
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Advisory Committee
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Ki-Bum Lee
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NamePart
(type = family)
Li
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Jing
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internal member
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Advisory Committee
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Jing Li
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Asefa
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Tewodros
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internal member
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Advisory Committee
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Tewodros Asefa
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NamePart
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Fabris
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Laura
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outside member
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Advisory Committee
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Laura Fabris
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NamePart
Rutgers University
Role
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degree grantor
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Graduate School - New Brunswick
Role
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school
OriginInfo
DateCreated
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2010
DateOther
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2010-10
Place
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(type = code)
xx
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
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(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Location
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3CZ36WF
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Jung
GivenName
Jongjin
Role
Copyright Holder
RightsEvent
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Type
Permission or license
DateTime
2010-09-29 00:08:30
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Name
Jongjin Jung
Affiliation
Rutgers University. Graduate School - New Brunswick
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License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
(ID = RE-2);
(AUTHORITY = rulib)
Type
Embargo
DateTime
2010-10-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 2nd, 2011.
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Technical
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ETD
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application/pdf
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application/x-tar
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5427200
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