Development and in vitro characterisation of a super-paramagnetic hybrid nanoparticle for multi-modal targeted drug delivery in pancreatic cancer



Sykes, PD
(2018) Development and in vitro characterisation of a super-paramagnetic hybrid nanoparticle for multi-modal targeted drug delivery in pancreatic cancer. PhD thesis, University of Liverpool.

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Abstract

Introduction Pancreatic cancer carries a poor prognosis despite improvement through the use of adjuvant chemotherapy. Nanotechnology offers the possibility for patient tailored therapy by providing novel methods of targeted drug delivery. Aim To develop a nanoparticle drug delivery vehicle capable of multi-modal targeted drug release Methods Hybrid nanoparticles (SpHyNs) were manufactured from superparamagnetic iron oxide cores and an amphiphilic polyoxazoline polymer shell using a self- assembly methodology. They were loaded with a gemcitabine prodrug, modified for release at low pH levels found in endosome. Multi-modal targeting using a cancer specific antibody and a focused magnetic field was assessed. Results SpHyNs were taken up into cells via endocytosis permitting use of a pH-dependent drug release mechanism. The cytotoxicity of targeted drug-laden SpHyNs was significantly increased against target positive cancer cells. Magnetically targeted drug release showed significant reduction in cell count at the area of greatest magnetic force. Conclusion We developed a superparamagnetic hybrid nanoparticle with multi-modal targeting capabilities and a novel drug-release mechanism. This could reduce off-target effects leading to increased chemotherapy agent efficacy and offer the prospect for new treatments in pancreatic cancer.

Item Type: Thesis (PhD)
Divisions: Fac of Health & Life Sciences > Institute of Translational Medicine
Depositing User: Symplectic Admin
Date Deposited: 28 Jun 2019 09:41
Last Modified: 09 Jan 2021 04:07
DOI: 10.17638/03035847
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3035847