Thesis

Safety optimisation of a hybrid nanoparticle based on thermo-responsive delivery system for pancreatic cancer treatment

Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2025
Thesis identifier
  • T17188
Person Identifier (Local)
  • 202161576
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Gold and silver coated iron oxide nanoparticles offer an ideal platform technology for theranostic application. Their ability as drug carriers to carry chemotherapeutic cargo has been evaluated and the next step is to ensure their safety before application clinically. Safety testing of nanoparticles presents a gap that needs to be filled for further progression especially in the clinical field. The work of this project seeks to address the safety and cytotoxicity testing of nanoparticles with different cell-based assays and thereby improve knowledge on this area. Gold-iron oxide hybrid nanoparticles (AuHNPs) and silver-iron oxide hybrid nanoparticles (AgHNPs) were successfully synthesised in Chapter 2 and characterisation analysis performed. The particle size of the naked NPs was measured to range from 50-100 nm with a spherical shape. AuHNPs and AgHNPs were also surface modified using Foetal Bovine Serum (FBS), a thermo-responsive polymer coating and a double coating of FBS and polymer. Physical and chemical stability studies of the synthesised NPs were conducted in Chapter 3. Aggregation was noted at differing timepoints. After 30 minutes, all NPs aggregated and settled at the bottom of the vials. The double-coated NPs (with FBS and polymer) stayed longest in solution before aggregation occurred. The NPs were observed to be chemically stable after ICP analysis as 0% release of gold or silver ions (no leaching) was observed. In vitro testing was carried out in Chapter 4 to test for the cytotoxicity of NPs in pancreatic cancer cells. AgHNPs exhibited the highest toxicity whilst AuHNPs were biocompatible and showed the least toxicity in the cells. The Trypan Blue assay that was performed revealed the lowest percentage cell viability for AgHNPs and LDH assay showed the highest percentage for LDH release in AgHNPs as well indicating high cytotoxicity. IC50 of the naked AuHNPs was 26.51 µg/mL whilst for the polymer-coated hybrids was 69.52 µg/mL (for the BxPC-3 cell line). This alludes to the fact the polymer that was used reduced cytotoxicity and therefore translating to improved biocompatibility. In vivo testing was also carried out over a 4-week period on nude mice in Chapter 5 to test for toxicity of synthesised AuHNPs. The mice did not display any signs of gross toxicity proving and confirming that the synthesised AuHNPs are safe to use and biocompatible in living organisms. Future work and further suggestions are discussed in the final Chapter 6.
Advisor / supervisor
  • Hoskins, Clare
Resource Type
DOI

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