Screening for effects of small molecules on cells grown in culture is a well-established method for drug discovery and testing,
and faster throughput at lower cost is needed especially for lipophilic materials. Small-molecule arrays present a promising approach.
However, it has been a challenge to use them to obtain quantitative surface based dose-response curves in vitro, especially for lipophilic
compounds. This thesis first introduces a simple novel method of surface-mediated delivery of drugs to cells from a microarray of
phospholipid multilayers (layers thicker than a bilayer) encapsulating small molecules. The capability of controlling the dosage of the
lipophilic molecules delivered to cells using the lipid multilayer microarray assay is further demonstrated using the nanointaglio
printing method. This control enabled the variation of the volumes of surface supported lipid micro- and nanostructure arrays fabricated
with nanointaglio. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated
by atomic-force microscopy. The surface supported lipid volume information was used to obtain EC-50 values for the response of HeLa cells
to treatment with three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be
significantly different from neat lipid controls. Features with sub-cellular lateral dimensions were found to be necessary to obtain
normal cell adhesion with HeLa cells. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally
from solution revealed quantitative differences in the efficacy values, which may be explained in terms of cell-adhesion playing a more
important role in the surface-based assay. Finally, solution encapsulation was done for a library of hydrophilic silicon nanocrystals in
order to set a solution standard for comparison with future surface supported delivery of the library. The work presented here opens the
door for the possible benchtop high throughput and high content screening of hydrophobic materials that were previously difficult or
impossible to readily screen. / A Dissertation submitted to the Department of Biological Science in partial fulfillment of the
requirements for the degree of in partial fulfillment of the Doctor of Philosophy. / Spring Semester 2016. / March 28, 2016. / Dose response, Drug screening, High throughput screening, Lipid multilayers, Microarray, Nanointaglio / Includes bibliographical references. / Steven Lenhert, Professor Directing Dissertation; Jingjiao Guan, University Representative;
Thomas Keller, Committee Member; Bryant P. Chase, Committee Member; Teng Ma, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_360392 |
| Contributors | Kusi-Appiah, Aubrey Emmanuel (authoraut), Lenhert, Steven (professor directing dissertation), Guan, Jingjiao (university representative), Keller, Thomas C. S. (committee member), Chase, P. Bryant (committee member), Ma, Teng (committee member), Florida State University (degree granting institution), College of Arts and Sciences (degree granting college), Department of Biological Science (degree granting department) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource (97 pages), computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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