Characterization of Triggerable Quinones for the Development of Enzyme-Responsive Liposomes
type: CreativeWork
description: For decades, there has been a lot of focus on the development of new carriers for drug delivery applications. From all of the carriers, stimuli-responsive liposomes have been studied extensively, but only a handful have been enzyme-responsive liposomes. Therefore, the field of endogenous proteins as activators of liposomes is a fertile field worthy of exploration. The research described in this dissertation involves how structural changes on the quinone moiety altered their electronic properties, as well as their behavior toward the human enzyme NAD(P)H:quinone oxidoreductase type-1 (hNQO1, over expressed in certain tumor tissues), thus yielding a series of triggerable quinones to be used in the formation of enzyme-activated liposomes. The step-wise process to achieve the ultimate research objective includes: (1) measurement by cyclic voltammetry of–the electronic properties of naked, propionic acid quinones and those attached to an ethanolamine handle, (2) detailed kinetics (Michaelis constant (Km), maximum velocity (Vmax), catalytic constant (kcat), enzyme efficiency (kcat/Km)) and computational docking studies for a series of quinone derivatives against hNQO1, and (3) preparation of quinone-based liposomes and evaluation in the presence of the different components included in an hNQO1 assay. Structural alterations on the quinone ring had an effect on their reduction behavior. Electrochemical studies exposed a trend in reduction potential; quinones with electron-withdrawing groups were easy to be reduced and the opposite happens to quinones with electron- donating groups. Enzyme and docking studies showed the different quinone responses obtained from the interaction of hNQO1 with structural-altered quinones. Liposome experiments provided all the obstacles that need to be overcome when designing an enzyme-responsive liposome system. The inclusion of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or cholesterol decreased the leakage of contents from the liposome sy…
abstract: For decades, there has been a lot of focus on the development of new carriers for drug delivery applications. From all of the carriers, stimuli-responsive liposomes have been studied extensively, but only a handful have been enzyme-responsive liposomes. Therefore, the field of endogenous proteins as activators of liposomes is a fertile field worthy of exploration. The research described in this dissertation involves how structural changes on the quinone moiety altered their electronic properties, as well as their behavior toward the human enzyme NAD(P)H:quinone oxidoreductase type-1 (hNQO1, over expressed in certain tumor tissues), thus yielding a series of triggerable quinones to be used in the formation of enzyme-activated liposomes. The step-wise process to achieve the ultimate research objective includes: (1) measurement by cyclic voltammetry of–the electronic properties of naked, propionic acid quinones and those attached to an ethanolamine handle, (2) detailed kinetics (Michaelis constant (Km), maximum velocity (Vmax), catalytic constant (kcat), enzyme efficiency (kcat/Km)) and computational docking studies for a series of quinone derivatives against hNQO1, and (3) preparation of quinone-based liposomes and evaluation in the presence of the different components included in an hNQO1 assay. Structural alterations on the quinone ring had an effect on their reduction behavior. Electrochemical studies exposed a trend in reduction potential; quinones with electron-withdrawing groups were easy to be reduced and the opposite happens to quinones with electron- donating groups. Enzyme and docking studies showed the different quinone responses obtained from the interaction of hNQO1 with structural-altered quinones. Liposome experiments provided all the obstacles that need to be overcome when designing an enzyme-responsive liposome system. The inclusion of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or cholesterol decreased the leakage of contents from the liposome sy…
author: Mendoza, Maria Fabiana
keywords: liposomes, enzyme, NQO1, molecular docking, drug delivery, quinones, cyclic voltammetry
date published: 2011-01-01T08:00:00Z
date modified: 2026-07-24T02:59:03Z
provider: Lousiana State University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Chemistry

PropertyValue
property ID: DOI
value: 10.31390/gradschool_dissertations.1173