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Pancreatic ductal adenocarcinoma (PDAC) is a deep seated and aggressive tumour which resists most current therapeutics resulting in only 5% survival rate. Gemcitabine, although the first line of treatment still has limited therapeutic value due to severe side effects. New treatment modalities are urgently required which efficiently deliver drugs to the target tumour area without causing adverse off-target side effects. We aimed to combine two clinical treatments for cancer, chemotherapy and RadioDynamic Therapy (RDT), to overcome current treatment for PDAC. In this project, specially designed nanoparticles (NP) were utilised as nanodrug carriers. Our poly(lactic-co-glycolide) (PLGA) nanoparticles were successfully loaded with both chemotherapeutic agent Gemcitabine and RDT agent Verteporfin. Addition surface conjugation with GE11 peptide allowed to precisely target Panc-1 cancer cell lines overexpressing EGFR receptors. Our results show PLGA was successfully fine-tuned with desirable physicochemical properties. Gemcitabine and Verteporfin were sufficiently loaded into the PLGA NP and surface conjugation with GE11 peptide was confirmed using absorbance spectroscopy. The resulting GE11-PLGA-VP-GEM NPs showed size 86.38±15 nm, polydispersity 0.57±0.1 and zeta potential measurements of -2.87±1 mV. Encapsulation efficiency (EE) was determined to be 20% for Verteporfin and 24% for Gemcitabine. This combination offers a multimodal treatment system whereby Gemcitabine is able to be effectively delivered to Panc-1 cells and, simultaneously, Verteporfin, induced by Xray radiation generates ROS to cause cell death. Cellular uptake studies were evaluated and the treatment of live Panc-1 cells with GE11-PLGA-VP-GEM NP induced cell death. Furthermore, Verteporfin, excited at clinically relevant X-ray dosages generated ROS.
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