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Polymer-gold nanoparticulate formulations for combinational photochemotherapy of pancreatic cancer

Emamzadeh, Mina; (2018) Polymer-gold nanoparticulate formulations for combinational photochemotherapy of pancreatic cancer. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Pancreatic cancer is one of the most deadly of all types of cancer, with a yearly incident that equals its mortality. Gemcitabine (Gem) is currently the first-line chemotherapeutic drug used to treat pancreatic cancer. The major deficiencies of Gem therapy are poor cell membrane permeability, short plasma half-life and toxic side effects. In order to improve the pharmacokinetic characteristics and overcome the obstacles to achieve effective drug delivery, a nanoparticulate drug delivery system can be utilised; gold nanoparticles (GNPs) have been investigated as carriers for drug delivery due to their appealing physicochemical and optical properties. This research project concerns the development of a new generation of GNPs for cancer treatment by co-delivering anti-cancer drugs in combination with laser-induced photothermal effects confined at the diseased areas. Gold nanoshells (GNShells) were synthesised with the capability to carry and deliver Gem and exert phototherapeutic properties. Protein repellent thiol capped poly (ethylene glycol) methyl ether methacrylate polymers were synthesised by RAFT polymerisation and used as efficient particle stabilising ligands. Significant stability enhancement was achieved allowing for the co-functionalisation of GNShells with Gem for applications in in vitro assays against pancreatic cancer cells. GNShells mediated strong photothermal effect owing to their strong surface plasmon absorption in the red/NIR region. This property was exploited to enhance the toxicity of Gem using laser light as the external stimulus. The concerted antitumor activity of Gem with the photothermal effect of the GNShells upon irradiation with a continuous wave laser, increase the cellular uptake and efficacy of Gem-loaded GNShells against MiaPaCa-2 cells. Therefore, the proposed nanoformulation might provide an active strategy for synergistic chemo-photothermal combined therapy.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Polymer-gold nanoparticulate formulations for combinational photochemotherapy of pancreatic cancer
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
URI: https://discovery.ucl.ac.uk/id/eprint/10059498
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