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Title: Self-assembled oligopeptide nanostructures for anticancer drug and/or gene delivery
Keywords: Oligopeptide self-assembly, cationic micelle, co-delivery, p53, cancer therapy, galactose targeting ligand
Issue Date: 18-Aug-2009
Citation: NIKKEN WIRADHARMA (2009-08-18). Self-assembled oligopeptide nanostructures for anticancer drug and/or gene delivery. ScholarBank@NUS Repository.
Abstract: Development of biomaterials for delivery of therapeutic molecules has emerged from the past few decades. Ideally such carrier materials should be biodegradable, non-cytotoxic, non-immunogenic, and at the same time capable to deliver the therapeutic molecules to its target sites. This thesis focuses on the development of self-assembled amphiphilic oligopeptides forming core-shell nanostructures for efficient delivery of genes and/or drugs. The first part of this thesis was aimed to design an efficient gene delivery vector in the form of self-assembled oligopeptide nanoparticles. Basic material characterizations were performed to evaluate the suitability of the materials as gene carrier. Its efficacy in inducing transgene expression was also tested with various cell lines in vitro. Following that, systematic tailoring of the hydrophobic tail of the oligopeptides was demonstrated to fine-tune and achieve desired properties of the vehicle for simultaneous delivery of drug and gene application. Its versatility was also demonstrated with its capability to deliver gene, drugs, or both simultaneously. Simultaneous delivery of both p53-encoding plasmid and doxorubicin, as the anticancer agents was then demonstrated with the self-assembled peptide carrier. A study with a liver cancer HepG2 cell line showed that the combination of these therapeutic molecules evidently achieved increased cytotoxic effect against the cancer cell. Finally, a method of incorporating an active targeting ligand onto cationic micellar nanoparticles was presented. By designing a short peptide containing a negatively-charged block of amino acids and a galactose moiety, electrostatic coating of cationic micelles containing both drug (in the core) and gene (on the surface) with the peptide was made possible.
Appears in Collections:Ph.D Theses (Open)

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