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Design, synthesis, and utility of fuctionalized nanoscale amphiphilic macromolecules for biomedical applications

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Design, synthesis, and utility of fuctionalized nanoscale amphiphilic macromolecules for biomedical applications
Identifier
ETD_3120
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057691
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Micelles
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Macromolecules
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Biomedical materials
Subject (ID = SBJ-5); (authority = ETD-LCSH)
Topic
Polymers in medicine
Subject (ID = SBJ-6); (authority = ETD-LCSH)
Topic
Nanotechnology
Abstract (type = abstract)
Polymeric micelles are spherical assemblies of amphiphilic polymers widely studied for many biomedical applications. Nanoscale amphiphilic macromolecules (AMs) are novel amphiphilic polymers composed of an alkylated sugar backbone covalently linked to poly(ethylene glycol) (PEG). In aqueous solution, AMs self-assemble to form 10-20 nm micelles with critical micelle concentrations as low as 100 nM, making them more stable than other common micelles. In addition, the basic structure of AMs has multiple points of modification such that the polymer can be modified and evaluated for virtually any application. This work highlights the promise of functionalized AMs as a novel, versatile biomaterial. Carboxy-terminated AMs were previously shown to inhibit highly oxidized low- density lipoprotein (hoxLDL) uptake in macrophage cells. To gain a mechanistic understanding of this inhibition, a series of AMs were designed and synthesized by modifying the basic polymer structure to evaluate several characteristics including: amphiphilicity, PEG chain length, anionic charge location, type of anionic charge, number of anionic charges, rotational motion of the anionic group, and PEG architecture. The optimal AM for inhibiting hoxLDL uptake was determined to be one with a rigid, rotationally-restricted carboxylic acid within the hydrophobic portion of the polymer. Building upon previous work that showed AMs deliver cargo intracellulary, a series of cationic polymers were designed and synthesized for nucleic acid delivery. The cationic moiety was added within the hydrophobic component of the AMs such that when the cationic portion complexed with anionic nucleic acids, the nucleic acids would be localized in the micellar interior. Three cationic AMs were evaluated with varying surface charges. The polymer with the highest surface charge was the most effective at complexing with and delivering small interfering RNA to U87 glioma cells. Finally, without modification, AMs are capable of water-solubilizing hydrophobic drugs. This property can be applied to hydrophobic fluorescent nanocrystals, which are useful for biological imaging. In the last chapter, AMs were utilized to water-solubilize white light-emitting nanocrystals without altering the emission properties of the nanocrystals. By modifying the polymer structure to incorporate functionalities that can coordinate to the surface of the nanocrystals, smaller, water-soluble assemblies that maintain white light-emission were obtained.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
xxvii, 170 p. : ill.
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application/pdf
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text/xml
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Sarah Marie Sparks
Name (ID = NAME-1); (type = personal)
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Sparks
NamePart (type = given)
Sarah Marie
NamePart (type = date)
1984-
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author
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Sarah Sparks
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
Uhrich
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Kathryn E
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chair
Affiliation
Advisory Committee
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Kathryn E Uhrich
Name (ID = NAME-3); (type = personal)
NamePart (type = family)
Seidel
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Daniel
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internal member
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Advisory Committee
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Daniel Seidel
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Warmuth
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Ralf
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internal member
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Advisory Committee
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Ralf Warmuth
Name (ID = NAME-5); (type = personal)
NamePart (type = family)
Moghe
NamePart (type = given)
Prabhas V
Role
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outside member
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Advisory Committee
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Prabhas V Moghe
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
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degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2011
DateOther (qualifier = exact); (type = degree)
2011-01
Place
PlaceTerm (type = code)
xx
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
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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/T31V5DND
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (AUTHORITY = GS); (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
Sparks
GivenName
Sarah
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2011-01-04 23:14:46
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
Role
Copyright holder
Name
Sarah Sparks
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
Type
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
2011-01-31
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after August 2nd, 2011.
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ETD
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application/pdf
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application/x-tar
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