101PDelivery of E-cadherin (CDH1) gene and epidermal growth factor receptor (EGFR) siRNA, using carbonate apatite as a promising vehicle in treatment of breast cancer

Background: E-cadherin (CDH1), a cell adhesion glycoprotein is widely associated with breast cancer where it is involved in tumor growth, invasion and metastasis. Down regulation of its gene is hall mark for epithelial-mesenchymal transition, which is an essential process for tumor metastasis. While various pathways are associated with E-cadherin, one of the prominent signaling pathways is via epidermal growth factor reception (EGFR), which is found to be over expressed. Silencing the over expressed EGFR gene by using a specific short-interfering RNA (siRNA), or inducing the expression of CDH1 gene with the help of a plasmid could improve management of malignant cancers by disturbing cancer cell interactions with adjacent cells and extracellular matrix; however, tumor-targeted delivery of these complexes is a major challenge in cancer therapy. This could be overcome by using pH-sensitive carbonate apatite nanoparticles that can enhance the intracellular delivery and release of the bound DNA or siRNA from endosomes to cytosol, after being transported to the tumor.