The development and evaluation of multifunctional silver iron-oxide hybrid nanoparticles towards enhanced pancreatic cancer therapy
Pancreatic cancer is the most aggressive of all common cancers and possesses high resistance to treatment, leading to poor survival outcomes. Lack of drug efficacy is a major issue faced by patients. The nanomedicine community are striving to develop innovative technologies, such as nanoparticle drug delivery systems, to address this issue. Multifunctional silver iron-oxide hybrid nanoparticles (AgHNPs) are presented as a thermo-responsive drug delivery system to improve pancreatic cancer therapy by reducing harsh systemic side effects of chemotherapy drugs and overcoming chemoresistance by the tumour environment and intratumoural bacteria, increasing drug accumulation in the tumour. This thesis reports the synthesis and characterisation of AgHNPs and the evaluation of their intrinsic properties for multifunctional synergistic applications in cancer therapy. To assess AgHNPs capability for use in thermally triggered formulations, the plasmonic properties were evaluated for heat generation at the particle surface. Upon irradiation with a femtosecond laser at 1040 nm, AgHNPs showed rapid heat generation (reaching temperatures around 40 °C in 5 s). The heat generation was localised and the particles did not show retention of the maximum temperature upon removal of irradiation. Surface functionalisation was successful with anti-cancer drug, 6-Thioguanine, and thermo-responsive polymers via thiol-silver bonding. The incorporation of a thermo-responsive coating was vital to allow for controlled exposure of the silver surface as AgHNPs exhibited anti-bacterial behaviour against Escherichia coli (a type of Gammproteobacteria commonly found in pancreatic tumours) and displayed inherent cytotoxic behaviour against pancreatic cancer cell line, BxPC-3, highlighting their potential as an anti-cancer agents within their own right, as well as drug carriers. This work delivered assessments on the multifunctional properties of AgHNPs which could be exploited to synergistically overcome the challenges currently impeding chemotherapeutic efficacy and poor patient prognosis. Herein a novel hybrid nanoparticle system is proposed for targeted and controlled treatment of pancreatic cancer.
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