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

The cationic polypropylenimine dendrimer DAB-Am16 forms stable complexes with shRNA and siRNA that are effectively taken up into cells. ITCH, an ubiquitin ligase, keeps cellular levels of the pro-apoptotic protein p73 low by ubiquitination which targets it for destruction in the proteasome. Down-regulation of the ITCH target gene reduces this activity thus sensitizing the cell/s for apoptotic signals. Pancreatic tumour xenografts can be controlled by sub-therapeutic doses of gemcitabine after sensitisation through systemic administration of anti-ITCH shRNA DAB-Am 16 gene therapy.223