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Receptor-targeted nanocarriers for tumor specific treatment and imaging
Descriptive
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Title
Receptor-targeted nanocarriers for tumor specific
treatment and imaging
treatment and imaging
Name
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Saad
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Maha
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Maha Saad
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author
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Minko
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Tamara
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Advisory Committee
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Tamara Minko
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chair
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You
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G.
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Advisory Committee
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G. You
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internal member
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michniak
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B.
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Advisory Committee
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B. michniak
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internal member
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Shahied
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S.
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Advisory Committee
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S. I. Shahied
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outside member
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Rutgers University
Role
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degree grantor
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Graduate School - New Brunswick
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school
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Text
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theses
OriginInfo
DateCreated
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2008
DateOther
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2008-10
Language
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English
PhysicalDescription
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electronic
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application/pdf
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text/xml
Extent
xviii, 193 pages
Abstract
Lung cancer is the leading cause of cancer death in the United States. The efficacy of chemotherapy in lung cancer is limited by the development of cancer cell resistance during the treatment, difficulties in the delivery of anticancer drugs specifically to lung tumors, and severe adverse side effects of high doses chemotherapy on healthy organs. The main objectives of the present research are: (1) to provide effective delivery of therapeutic and imaging agents to lungs, (2) to mitigate the above described resistance, (3) to enhance the efficacy of lung cancer chemotherapy and limit adverse side effects of the treatment. To achieve these goals, we developed, characterized, and evaluated in vitro and in vivo on orthotopic model of lung cancer using a novel multifunctional tumor-targeted Nanocarrier-based Drug Delivery System (NDDS) composed of (1) a carrier; (2) a synthetic analog of Luteinizing Hormone-Releasing Hormone (LHRH peptide) as a targeting moiety; (3) an anticancer drug or imaging agent; (4) suppressors of drug resistance. We tested and compared: linear polymer, dendrimers and liposomes as nanocarriers; antisense oligonucleotides or small interfering RNA targeted to MRP1 and BCL2 mRNA as suppressors of pump and nonpump cellular resistance respectively; near-infrared cyanine dye Cy5.5, rhodamine, or fluorescein isothiocyanate as imaging agents.
The proposed multivalent NDDS exhibited preferential accumulation in the lungs, increased the sensitivity and specificity of tumor imaging, enhanced cancer treatment, and limited adverse side effects of the treatment on healthy organs. Targeting of nanocarriers to tumor specific receptors minimizes the influence of the architecture, composition, size, and molecular mass of nanocarriers on the efficacy of imaging and cancer treatment.
Local intratracheal administration sustained higher concentration of NDDS and its payload in the lungs and substantially limited their accumulation in other organs. Moreover, intratracheal local delivery of NDDS led to the more efficient treatment of lung cancer when compared with the intravenous administration of NDDS or free drugs. Simultaneous suppression of pump and nonpump resistance dramatically enhanced the cytotoxicity of the anticancer drug leading to a substantial increase in apoptosis induction.
The proposed multivalent NDDS exhibited preferential accumulation in the lungs, increased the sensitivity and specificity of tumor imaging, enhanced cancer treatment, and limited adverse side effects of the treatment on healthy organs. Targeting of nanocarriers to tumor specific receptors minimizes the influence of the architecture, composition, size, and molecular mass of nanocarriers on the efficacy of imaging and cancer treatment.
Local intratracheal administration sustained higher concentration of NDDS and its payload in the lungs and substantially limited their accumulation in other organs. Moreover, intratracheal local delivery of NDDS led to the more efficient treatment of lung cancer when compared with the intravenous administration of NDDS or free drugs. Simultaneous suppression of pump and nonpump resistance dramatically enhanced the cytotoxicity of the anticancer drug leading to a substantial increase in apoptosis induction.
Note
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Ph.D.
Note
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Includes bibliographical references.
Subject
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Topic
Pharmaceutical Science
Subject
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Topic
Biotechnology
Subject
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Topic
Nanotechnology
Subject
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(authority = ETD-LCSH)
Topic
Drug delivery systems
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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rucore19991600001
Identifier
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.17560
Identifier
ETD_1105
Location
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NjNbRU
Identifier
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doi:10.7282/T36110MR
Genre
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ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
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Copyright protected
Availability
Status
Open
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Name
Maha Saad
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Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
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Non-exclusive ETD license
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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.
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