Hydrogel-nanoparticle patches as prophylactic scaf.. (CancerHydrogelPatch)
Hydrogel-nanoparticle patches as prophylactic scaffold agents for in vivo local gene/drug delivery in colorectal cancer tumours
Date du début: 1 mai 2014,
Date de fin: 30 avr. 2017
The World Health Organization and the American Cancer Society states that colorectal cancer is one of the most frequent cancers in Europe and in USA. Surgery is the primary form of treatment. Nevertheless, recurrence following surgery is a major problem and is often the ultimate cause of death. Previous therapies have not provided sufficient specificity and structural guidance to promote tumour inhibition after remission, as well as the full regeneration of injury tissue after surgery. Accordingly, our specific aim is to target colorectal tumours cells with hydrogels-drug-siRNA nanorods conjugates after surgery removal of the tumour in in vivo mice models of colorectal cancer. Drug conjugates (i.e. Bevacizumab, Cetuximab, Panitumumab) will be designed to specifically target cancer related growth factor receptors. These drugs will be associated with siRNA molecules against key genes in colorectal cancer progression (EpHB2, EGFR, Wnt) that will be specifically and local delivered in tumour cells. The ultimate goal of the project is to create a sort of patch made of the bioresorbable biomaterial like hydrogels impregnated with drug-siRNA conjugates for locally release in colorectal tumoral cells. At the same time, the hydrogel-nanoparticles functionalized with adhesion proteins like collagen, fibronectin and RGD will be designed as a scaffold with a polymeric core and an adhesive shell for enhanced attachment, proliferation, and phenotypic maintenance of intestinal endothelial and stem cells, as well as for the release of growth factors like insulin and EGF. To the best of our knowledge, this is the first time that a multi-parallel solution to in vivo gene/drug delivery combined to soft tissue engineering applications to promote endothelial and stem cell adhesion, proliferation and migration is proposed. This proposal achieves the aims of the European Research Area and is highly relevant to the Marie Curie Programme and to long-term carreer development.
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