Malekigorji, Maryam (2016) Preparation and evaluation of hybrid gold-iron oxide nanoparticles as a multifunctional platform for diagnosis and therapy of pancreatic cancer. Doctoral thesis, Keele University.

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the most common epithelial, exocrine pancreatic malignancy. Gemcitabine, as the only chemotherapy clinically available for pancreatic cancer, proves effective only in 23.8% of patients. Recently, iron oxide-gold hybrid nanoparticles (HNPs) have received significant attention in cancer therapy, which exploit the surface chemistry and SPR of the gold with magnetic character of the iron oxide, offering imaging, heating and drug delivery potentials.

In this work HNPs were synthesised using a multi-step coating process of iron oxide cores. Particles were characterised by different techniques, in terms of their size, zeta potential, morphology and their magnetic properties. Laser irradiation on HNPs was used in order to obtain optimal temperature increase, needed for drug release. It is postulated that nanoparticulate irradiation at lower temperatures can trigger drug release from the surface of the vehicle before cellular hyperthermia was initiated. Different bisnaphtalamide based anticancer drugs were conjugated onto the surface of the HNPs. Drug loading, stability and drug release studies were carried out. A pancreatic cancer targeting peptide (c(RGDfC)) was conjugated to the formulations to increase drug specific delivery and anticancer activity. In vitro biological studies were performed on two pancreatic cancer cell lines and a human monocyte cell line.

Hybrid formulations (specially targeted formulation) have shown higher cytotoxicity compared with free drugs and gemcitabine on pancreatic cancer cells. Drug uptake pattern was dose responsive and time dependant on all cell lines, and hybrid formulations internalised at significantly higher concentrations than the free drugs. AFM topography images were in agreement with cellular uptake. Moreover, HNPs possessed thermoresponsive drug delivery potentials in vitro.

This is the first time these novel drugs were conjugated to iron oxide-gold HNPs, which demonstrated the interesting potential of these nanoparticles to act as thermoresponsive drug carriers.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: Iron oxide-gold nanoparticles, Pancreatic cancer, Thermoresponsive drug delivery
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Lisa Bailey
Date Deposited: 12 Apr 2017 13:26
Last Modified: 28 Apr 2017 01:30
URI: http://eprints.keele.ac.uk/id/eprint/3245

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