A nano-enabled cancer-specific ITCH RNAi chemotherapy booster for pancreatic cancer

Publication date: Available online 6 October 2014 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Maria de la Fuente , Marie-Christine Jones , Manuel J. Santander-Ortega , Anja Mirenska , Preethi Marimuthu , Ijeoma Uchegbu , Andreas Schätzlein Gemcitabine is currently the standard therapy for pancreatic cancer. However, growing concerns over gemcitabine resistance mean that new combinatory therapies are required to prevent loss of efficacy with prolonged treatment. Here, we suggest that this could be achieved through co-administration of RNA interference agents targeting the ubiquitin ligase ITCH. Stable anti-ITCH siRNA and shRNA dendriplexes with a desirable safety profile were prepared using generation 3 poly(propylenimine) dendrimers (DAB-Am16). The complexes were efficiently taken up by human pancreatic cancer cells and produced a 40-60% decrease in ITCH RNA and protein expression in vitro (si/shRNA) and in a xenograft model of pancreatic cancer (shRNA). When co-administered with gemcitabine (100mg/kg/week) at a subtherapeutic dose, treatment with ITCH-shRNA (3x 50mg/week) was able to fully suppress tumour growth for 17days, suggesting that downregulation of ITCH mediated by DAB-Am16/shRNA sensitizes pancreatic cancer to gemcitabine in an efficient and specific manner. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research