Study On The Acidic Ph-induced Charge-reversal Nanocapsules For The Treatment Of Esophageal Cancer

Esophageal cancer is one of the most common malignant tumor of digestive system, accounting for the sixth place of cancer mortality in the world. The formation of esophageal cancer is caused by a comprehensive process of multi step and multi factor. Esophageal cancer is lack of effective treatment, and early symptoms are not obvious, so the prognosis of most patients is poor. At present, surgical therapy, chemotherapy and radiotherapy are mainly used for the treatment of esophageal cancer. Esophageal cancer carries high risk of recurrence and is lack of effective therapeutic drugs, which results in low 5 years survival rate. Therefore, the development of low toxicity, efficientand tumor-targeting medicine becomes one of the hotspots of esophageal cancer treatment. With the rapid development of nanotechnology, developing new anti-esophageal nanomedicine gradually become a new trend in drug research. It has great significance for reducing the incidence and mortality of esophageal cancer.MicroRNAs(miRNAs) are single-stranded non-coding RNA molecules of 20-25 nucleotides, which bind to the 3’-untranslated region(3’-UTR) of mRNA through partial base-pairing and result in degradation and translation suppression of their target mRNAs. The dysregulation of miRNA expression has been found to be closely associated with carcinogenesis. MiR-203 is a sort of microRNA derived from basal cell, it has been paid more attention because of its expression and tumors are highly correlated. Research has shown that miR-203 inhibits the proliferation and migration of tumor cells by inhibiting the expression of Ran, E2F1, LASP-1 and other target proteins, which play important roles in cell cycle and apoptosis.Currently, research on microRNA-based medicine is an attractive field. The transmembrane ability of microRNA is poor, and it is biodegradable easily in vivo, the development of delivery vehicle is thus very important. In the present study, pH-responsive nanocapsules were generated through self-assembly approach by using zwitterionic O-carboxymethy chitosan(CMC) and TAT peptide for miR-203 encapsulation. The resulting nanocapsules were investigated for the pH responsive charge-reversal property as well as endosomal escape for cytoplasmic release of miR-203, responsible for the regulation of the proliferation and migration of cancer cells. A series of experiments show that miR-203 can be delivered to cancer cells efficiently and released into the cytoplasmrapidly. Restoration of miR-203 expression in cancer cells can dramatically inhibit cell proliferation and migration through targeting GTPase Ran, E2F1 and LASP-1. This study investigates the mechanism and effect of pH-responsive nanocapsules in the inhibition of esophageal cancer cells, providing a new way for the treatment of esophageal cancer.