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Macrophage targeting using nanotechnology for HIV therapy
Descriptive
TitleInfo
Title
Macrophage targeting using nanotechnology for HIV therapy
Name
(type = personal)
NamePart
(type = family)
Chen
NamePart
(type = given)
Pei-Ming
DisplayForm
Pei-Ming Chen
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Sinko
NamePart
(type = given)
Patrick John
DisplayForm
Patrick John Sinko
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Suh
NamePart
(type = given)
Nanjoo
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Nanjoo Suh
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
You
NamePart
(type = given)
Guofeng
DisplayForm
Guofeng You
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Prud'homme
NamePart
(type = given)
Robert Kraft
DisplayForm
Robert Kraft Prud'homme
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)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-10
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Macrophages (MΦ) are involved in a number of pathological conditions, such as HIV infection/AIDS, tuberculosis, tumor development and atherosclerosis. The macrophage mannose receptor (MR) is expressed on the cell surface of tissue MΦ where it mediates the internalization of glycoproteins and glycoconjugates via both the endocytic and phagocytic pathways. The theme of the current study is to develop a nano-sized therapeutic delivery system that targets the MΦ MR. A series of mannosylated NCs were designed and synthesized to systematically evaluate the effects of mannose copy number, mannose ligand spacing and poly (ethylene glycol) (PEG) size on NC uptake via MR. Targeted nanocarriers (NCs) bearing mannose moieties were evaluated for targeting in MΦ cell lines. The first study demonstrated three important structural requirements for optimal mannose-targeted NC cellular uptake - two copies of the targeting ligand mannose were required, a 46.5 Å PEG spacer in between ligands was optimal and 12 kDa PEG size. Furthermore, the effect of MΦ polarization on NC uptake was also investigated. Rat peritoneal MΦs were polarized into classically activated (M1) and alternatively activated (M2a) phenotypes. The Western blot results showed the highest expression of MR on the M2a phenotype. Using confocal microscopy and a fluorescence microscope, 12-fold higher uptake of NC (2 copy mannose) was observed in M2aMΦ as compared to M1MΦ, suggesting great potential in selective MΦ cellular targeting. Drug-loaded NCs were prepared using a nucleoside reverse transcriptase inhibitor (AZT) or a protease inhibitor (RTV) conjugated to a NC with 2 copies of mannose linked by a PEG12 (46.5 Å) spacer. Anti-HIV activities of the drug conjugated NCs were assessed using U937/HIV-2MS cells and HIV-1 infected human monocyte derived MΦs and were based on a reduction in viral matrix protein p24 production. The results showed significant p24 reduction with EC50’s ranging from 5.7 uM to 25 uM indicating significant anti-HIV activity. Taken together, the studies presented in this dissertation identified the optimum configuration of drug loaded NCs for targeting the MΦ MR. Furthermore, the positive anti-HIV activities suggest that the NC approach holds great promise for receptor targeted drug delivery to HIV-infected MΦs.
Subject
(authority = RUETD)
Topic
Pharmaceutical Science
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_4296
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
x, 120 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Pei-Ming Chen
Subject
(authority = ETD-LCSH)
Topic
Macrophages
Subject
(authority = ETD-LCSH)
Topic
Drug delivery systems
Subject
(authority = ETD-LCSH)
Topic
HIV infections--Treatment
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066651
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T3P55M8Z
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Chen
GivenName
Pei-Ming
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(qualifier = exact);
(point = start)
2012-10-03 13:21:40
AssociatedEntity
Name
Pei-Ming Chen
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
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
DateTime
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(point = start)
2012-10-31
DateTime
(encoding = w3cdtf);
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(point = end)
2014-10-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 31st, 2014.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
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16337408
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application/pdf
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16343040
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