IDENTIFICATION OF EPITHELIAL OVARIAN TUMOR SPECIFIC APTAMERS THAT BIND AND INTERNALIZE INTO TARGET CELLS

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Benedetto, G. (2015). IDENTIFICATION OF EPITHELIAL OVARIAN TUMOR SPECIFIC APTAMERS THAT BIND AND INTERNALIZE INTO TARGET CELLS. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

New clinical tools that aid in the early diagnosis of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. The objective of the work presented here was to identify ovarian tumor specific single stranded DNA probes termed aptamers that bind to cell surface structures with high affinity and specificity. First I identified aptamers using a random screening protocol known as Cell-SELEX that bind and internalize to target cells. All aptamers identified demonstrate unique binding kinetics and internalized by the endocytic pathway. Next I assessed the internalization kinetics of identified aptamers when used to label the surface of polymeric organic nanoparticles. I was able to demonstrate that the high specificity exhibited by aptamers promotes localization and uptake of tethered nanoparticles by specific cell populations. Finally a preliminary pilot study looking at the in vivo stability of aptamers and their ability to promote retention and honing of nanoparticles at tumors was conducted. The experiments described here demonstrate the effective combinatorial use of aptamer and nanoparticle technologies for the direct targeting of tumor cell populations.

Details
Author

Benedetto, Gregory

Title

IDENTIFICATION OF EPITHELIAL OVARIAN TUMOR SPECIFIC APTAMERS THAT BIND AND INTERNALIZE INTO TARGET CELLS

Physical Description

1 online resource (253 pages) : PDF

Date

2015

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

New clinical tools that aid in the early diagnosis of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. The objective of the work presented here was to identify ovarian tumor specific single stranded DNA probes termed aptamers that bind to cell surface structures with high affinity and specificity. First I identified aptamers using a random screening protocol known as Cell-SELEX that bind and internalize to target cells. All aptamers identified demonstrate unique binding kinetics and internalized by the endocytic pathway. Next I assessed the internalization kinetics of identified aptamers when used to label the surface of polymeric organic nanoparticles. I was able to demonstrate that the high specificity exhibited by aptamers promotes localization and uptake of tethered nanoparticles by specific cell populations. Finally a preliminary pilot study looking at the in vivo stability of aptamers and their ability to promote retention and honing of nanoparticles at tumors was conducted. The experiments described here demonstrate the effective combinatorial use of aptamer and nanoparticle technologies for the direct targeting of tumor cell populations.

Genre

doctoral dissertations

Subjects--Topics

Chemistry
Biology

Degree

Ph.D.

Keywords

Aptamers
Cell-Selex
Nanoparticles
Ovarian Cancer
Targeted-Delivery
Targeted-Drug Therapy

Subject Area

Biology

Advisor(s)

Richardson, Christine

Committee Members

Schrum, Laura
Nelson, Daniel
Dreau, Didier
Fodor, Anthony

Degree Note

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2015.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Benedetto_uncc_0694D_10790

Permalink

http://hdl.handle.net/20.500.13093/etd:1483