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Nanomaterials for regulating cancer and stem cell fate

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TitleInfo
Title
Nanomaterials for regulating cancer and stem cell fate
Name (type = personal)
NamePart (type = family)
Shah
NamePart (type = given)
Birju P.
NamePart (type = date)
1983-
DisplayForm
Birju Shah
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Lee
NamePart (type = given)
Ki-Bum
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Ki-Bum Lee
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Uhrich
NamePart (type = given)
Kathryn
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Kathryn Uhrich
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Warmuth
NamePart (type = given)
Ralf
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Ralf Warmuth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Suh
NamePart (type = given)
Nanjoo
DisplayForm
Nanjoo Suh
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The realm of nanomedicine, defined as the applications of nanotechnology for medical purposes such as diagnosis, monitoring and treatment of diseases, has grown exponentially over the past few decades; with several research efforts translating into commercial success stories. Such applications requires the amalgamation of research efforts from different disciplines such as chemistry, biology, physics, engineering and clinical medicine. While the earlier efforts in nanomedicine were focused mainly on improving the properties of the available therapeutics, current research efforts are more geared towards developing novel therapeutics or imaging modalities based on the supramolecular assembly of nanoscale building blocks. There is a plethora of nanoscale platforms that are being developed for clinical uses, including, polymeric nanoparticles, liposomes and micelles, metallic nanostructures, semiconductor quantum dots and silicon oxide nanoparticles. However, there are several obstacles that need to be overcome, prior to the wide-spread clinical applications of these nanoparticles, such as (i) developing well-defined nanoparticles of varying size, morphology and composition to enable various clinical applications; (ii) optimization of the biopharmaceutical properties such as physiological stability, solubility and systemic circulation of the nanoparticle-based therapeutics; (iii) delivery of different kinds of therapeutics without altering their pharmacological effects; (iv) overcome various physiological barriers encountered in order to deliver the therapeutics to the target location; and (v) real-time monitoring of the nano-therapeutics within the human body for tracking their uptake, localization and effect. Hence, this dissertation focuses on developing multimodal nanotechnology-based approaches to overcome the above-mentioned challenges by combining either different nanoparticle compositions or different therapeutic moieties, towards a singular purpose of regulating cancer and stem cell fate, such as proliferation, differentiation and cell death. The initial part of this dissertation describes the synthesis and characterization of well-defined and monodisperse multimodal magnetic core-shell nanoparticles (MCNPs), comprised of a highly magnetic core surrounded by a thin gold shell. As a result of combining two different elements (Fe and Au) within a single nanoplatform, these multimodal core-shell nanoparticles possessed both magnetic and plasmonic properties, which allowed for enhanced therapy and imaging. These nanoparticles were utilized for mainly two applications: (i) Magnetically-facilitated delivery of siRNA and plasmid DNA to neural stem cells for inducing neuronal differentiation and non-invasive imaging and (ii) Combined hyperthermia and targeted delivery of a mitochondria-targeting peptide for enhancing apoptosis in brain and breast cancer cells. The following part of this dissertation presents the synthesis and applications of a multi-functional polymeric delivery platform (known as DexAMs), composed of a dendritic cationic polyamine conjugated to a single beta-cyclodextrin moiety. The DexAM molecule was utilized as a single vehicle to simultaneously deliver two orthogonal therapeutics - anticancer drugs and siRNAs against oncogenes, in a target-specific manner to brain tumor cells. This combined delivery of chemotherapeutics and siRNA targeted the multiple dysregulated pathways in cancer cells and this resulted in a synergistic effect on the apoptosis of brain tumor cells, as compared to the individual treatments. The final part of this thesis presents synthesis of stimuli-responsive fluorescence resonance energy transfer (FRET)-based mesoporous silica nanoparticles for real-time monitoring of drug release in cells. These MSNs were composed of a porous silica support which allowed for drug loading, a stimuli-responsive valve composed of disulfide bonds, and a FRET donor-acceptor pair of coumarin and fluorescein integrated within the disulfide bond. The stimuli-responsive valve was cleaved only in the presence of increased glutathione concentrations found within cancer cells, resulting in change in the FRET signal, thus allowing for real time monitoring of drug release. Taken together, these nanomaterial-based approaches combine therapeutic and imaging modalities within a single nanoplatform and as a result have the potential for regulating cancer and stem cell fate such as proliferation, differentiation and apoptosis as well as allowing for real-time monitoring of these events in a non-invasive manner.
Subject (authority = RUETD)
Topic
Chemistry and Chemical Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5475
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xvi, 199 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Birju P. Shah
Subject (authority = ETD-LCSH)
Topic
Nanomedicine
Subject (authority = ETD-LCSH)
Topic
Nanostructured materials
Subject (authority = ETD-LCSH)
Topic
Cancer--Treatment
Subject (authority = ETD-LCSH)
Topic
Stem cells--Research
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3CZ35GN
Genre (authority = ExL-Esploro)
ETD doctoral
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RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Shah
GivenName
Birju
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-04-13 14:21:49
AssociatedEntity
Name
Birju Shah
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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License
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Author Agreement License
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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.
Copyright
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Copyright protected
Availability
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windows xp
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