Development of Multifunction Nanoparticle for Gastric Cancer Therapy in vitro and in vivo

• Main Authors: Zih-Rou Chen, 陳紫柔
• Other Authors: 林宥欣
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/d96fmh

碩士 === 中國醫藥大學 === 生物科技學系碩士班 === 102 === Gastric cancer is one of the most common cancers, and over seventy percent of gastric cancers occur in developing countries. Various chemotherapy drugs, such as 5-fluorouracil, doxorubicin, and cisplatin, are used to treat gastric cancer. However, unpleasant side effects from these drugs may cause a patient to interrupt the prescribed course of chemotherapy. Thus, the development of new anti-cancer therapies or drugs with fewer side effects is highly desirable. Epigallocatechin-3-gallate is the most abundant of the tea catechins and, by virtue of its peculiar stereochemical structure, possesses antioxidant activity which allows it to play an important role in preventing cancer and cardiovascular disease. Epigallocatechin-3-gallate can also induce apoptosis in several types of cancer cells, with the apoptosis-inducing activity of the compound being dependent on its polyphenolic structure. It has previously been reported that epigallocatechin-3-gallate could reduce vascular endothelial growth factor production and inhibit the transcriptional expression level for gastric cancer. However, due to digestive instability and poor intestinal uptake/transport, the therapeutic potential of epigallocatechin-3-gallate is limited by its poor absorption following oral administration. In order to localize epigallocatechin-3-gallate on the gastric epithelium and thereby improve the efficacy of this anti-gastric cancer therapy, a novel epigallocatechin-3-gallate–loaded fucose-chitosan/polyethylene glycol-chitosan/gelatin nanoparticle delivery system has been developed. This nanonparticle delivery system can protect the epigallocatechin-3-gallate from gastric acids or enzymes, allowing it to target and destroy gastric cancer on the gastric epithelium. In our study, analysis of a simulated gastric and surface epithelial cell medium indicated that the nanoparticles can effectively control the release of epigallocatechin-3-gallate, such that it interacts specifically at the site of cancer cells, significantly increasing the epigallocatechin-3-gallate’s effectiveness in suppressing gastric cancer cell growth. We also used annexin V staining and flow cytometry to demonstrate that epigallocatechin-3-gallate–loaded nanoparticles which can induce apoptosis in gastric cells. Finally, it was found that epigallocatechin-3-gallate–loaded nanoparticle treatment significantly inhibited gastric tumor growth in an animal model in comparison to an epigallocatechin-3-gallate solution. These results revealed that the oral administration of fucose-chitosan/polyethylene glycol-chitosan/gelatin/ epigallocatechin-3-gallate nanoparticles could target gastric cancer cells through controlled drug release in order to inhibit gastric cancer cell growth.