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PH-responsive amphiphilic macromolecules for anticancer drug and siRNA delivery
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Gu, Li. PH-responsive amphiphilic macromolecules for anticancer drug and siRNA delivery. Retrieved from https://doi.org/doi:10.7282/T36Q1V9Z

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TitlePH-responsive amphiphilic macromolecules for anticancer drug and siRNA delivery
NameGu, Li (author); Uhrich, Kathryn (chair); Warmuth, Ralf (internal member); O'Carroll, Deirdre (internal member); Roth, Charles (outside member); Rutgers University; Graduate School - New Brunswick
Date Created2014
Other Date2014-01 (degree)
SubjectChemistry and Chemical Biology, Macromolecules, Drug delivery systems, Cancer--Treatment, Small interfering RNA
Extentxiv, 106 p. : ill.
DescriptionAmphiphilic macromolecules (AMs), composed of a macromolecular hydrophobic segment and a hydrophilic poly(ethylene glycol) (PEG) are used as drug delivery systems and therapeutics. In this dissertation, AMs maintained physicochemical and biological properties after commercial sterilization treatment indicating AMs are suitable for commercialization. Furthermore, AMs are modified for anticancer drug and siRNA delivery. In this dissertation, pH-sensitive AMs were successfully synthesized to solve the dilemma between stability during circulation and quick drug release at target site. Critical micelle concentrations of the pH-sensitive AMs indicated stability against dilution which occurs during blood circulation. Doxorubicin (DOX) was chosen as the anticancer drug to investigate the pH-dependent drug release profile. Enhanced DOX release at pH 5 was compared to pH 7.4 due to the cleavage of hydrazone in the AM backbone. Further cytotoxicity studies showed that pH-senstive AMs decreased cell viability compared to free DOX and controll micelles. Therefore, the pH-sensitive AMs can achieve both stability in physiological condition and quick drug release at target site. The delivery of short interfering ribonucleic acid (siRNA), a potent gene knock-down therapeutic, is a main issue in biomedical field. In this dissertation, novel cationic amphiphilic macromolecule (CAM)-lipid complexes were developed with comparable transfection efficiency to Lipofectamin, a gold standard siRNA delivery vehicle in vitro. Dynamic light scattering indicated that CAM-lipid complexes possess the pH-responsive features: stable at pH 7.4 (physiological pH) and instable at pH 5 (endosomal pH). Intracellular trafficking demonstrated the endosomal escape of siRNA possibly because of the pH-responsive feature. Furthermore, this dissertation is the first example of using isothermal titration calorimetry to study siRNA release from polymer-liposome systems. Overall, CAM-lipid complex was developed as an efficient siRNA carrier in vitro and mechanistic insights in delivery process provided.
NotePh.D.
NoteIncludes bibliographical references
Noteby Li Gu
Genretheses, ETD doctoral
Persistent URLhttps://doi.org/doi:10.7282/T36Q1V9Z
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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