Cholera Toxin Subunit B-Mediated Intracellular Trafficking of Mesoporous Silica Nanoparticles Toward the Endoplasmic Reticulum

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Walker, W. (2015). Cholera Toxin Subunit B-Mediated Intracellular Trafficking of Mesoporous Silica Nanoparticles Toward the Endoplasmic Reticulum. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

In recent decades, pharmaceutical research has led to the development of numerous treatments for human disease. Nanoscale delivery systems have the potential to maximize therapeutic outcomes by enabling target specific delivery of these therapeutics. The intracellular localization of many of these materials however, is poorly controlled, leading to sequestration in degradative cellular pathways and limiting the efficacy of their payloads. Numerous proteins, particularly bacterial toxins, have evolved mechanisms to subvert the degradative mechanisms of the cell. Here, we have investigated a possible strategy for shunting intracellular delivery of encapsulated cargoes from these pathways by modifying mesoporous silica nanoparticles (MSNs) with the well-characterized bacterial toxin Cholera toxin subunit B (CTxB). Using established optical imaging methods we investigated the internalization, trafficking, and subcellular localization of our modified MSNs in an in vitro animal cell model. We then attempted to demonstrate the practical utility of this approach by using CTxB-modified mesoporous silica nanoparticles to deliver propidium iodide, a membrane-impermeant fluorophore.

Details
Author

Walker, William

Title

Cholera Toxin Subunit B-Mediated Intracellular Trafficking of Mesoporous Silica Nanoparticles Toward the Endoplasmic Reticulum

Physical Description

1 online resource (57 pages) : PDF

Date

2015

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

In recent decades, pharmaceutical research has led to the development of numerous treatments for human disease. Nanoscale delivery systems have the potential to maximize therapeutic outcomes by enabling target specific delivery of these therapeutics. The intracellular localization of many of these materials however, is poorly controlled, leading to sequestration in degradative cellular pathways and limiting the efficacy of their payloads. Numerous proteins, particularly bacterial toxins, have evolved mechanisms to subvert the degradative mechanisms of the cell. Here, we have investigated a possible strategy for shunting intracellular delivery of encapsulated cargoes from these pathways by modifying mesoporous silica nanoparticles (MSNs) with the well-characterized bacterial toxin Cholera toxin subunit B (CTxB). Using established optical imaging methods we investigated the internalization, trafficking, and subcellular localization of our modified MSNs in an in vitro animal cell model. We then attempted to demonstrate the practical utility of this approach by using CTxB-modified mesoporous silica nanoparticles to deliver propidium iodide, a membrane-impermeant fluorophore.

Genre

masters theses

Subjects--Topics

Materials science
Nanoscience
Biomedical engineering

Degree

M.S.

Keywords

Cholera Toxin
Mesoporous Silica
Nanomedicine

Subject Area

Chemistry

Advisor(s)

Vivero-Escoto, Juan

Committee Members

Dréau, Didier
Troutman, Jerry
Krueger, Joanna

Degree Note

Thesis (M.S.)--University of North Carolina at Charlotte, 2015.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Walker_uncc_0694N_10877

Permalink

http://hdl.handle.net/20.500.13093/etd:1400