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Title: Delivery, interaction and fate of peptidecapped gold nanoparticles in mammalian cells
Author: Shaheen, Umbreen
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2012
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Cytosolic targeted delivery of molecular therapeutics is a crucial requirement to assess the efficacy and therapeutic potential of drugs. Recently, nanocarriers due to their easy and multidimensional use have been warmly welcomed by the scientific community, actively involved in designing delivery systems for in vivo/in vitro application. However, the endosomal entrapment of almost all types of nanoparticle-based delivery vehicles is a significant limitation. At present, most of the available non-viral and non-invasive delivery systems have shown modest results in addressing this problem. Gold nanoparticles are an interesting model system due to ease of functionalization, reduced toxicity and optical properties. Here viral peptides (HA2 or/and TAT) and bacterial toxin assisted delivery strategies have been employed for cytosolic delivery of the peptide or mix monolayer of peptide and PEGcapped gold nanoparticles. HA2 functionalized gold nanoparticles were seen to interact with the endosomal membranes, but did not disperse into the cytosol. However, the presence of HA2 peptide at the surface of gold nanoparticles increased the overall cellular uptake of gold nanoparticles and this trend was found to depend upon the coverage density of HA2 peptide. Similar results were obtained for several HA2 analogues. The pore forming bacterial toxin SLO was used to deliver the peptide and lor CCALNN-PEGcapped gold nanoparticles. Increased endocytosis of moderately PEGylated gold nanoparticles, but no cytosolic localization was observed by either gold nanoparticle imaging/e., optical microscopy (photothermal) or electron microscopy. Surprisingly, the membrane impermeable dextran polymers of up to 150 KDa sizes were successfully delivered to the cytosol of SLO treated cells. Finally, a pH sensitive polymer nanoparticle based delivery system (hydrogel) was employed for intracellular delivery of gold nanoparticles. The polymer particles decorated with evenly and sparsely present PEGylated CALNN-capped gold nanoparticles were localized to the cytosol, but gold nanoparticles were not able to detach from the hydrogels. The hydrogel inside the endosomal vesicles expanded in volume, but were not able to break the endosomes and release the attached gold nanoparticles.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available