Development of a novel cell penetrating peptide based biomaterial for epithelial tumor targeting

• Main Authors: Liu, Yu-Shiuan, 劉于瑄
• Other Authors: Chang, Dah-Tsyr
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/wyruv7

碩士 === 國立清華大學 === 分子與細胞生物研究所 === 103 === Glycosaminoglycan (GAG) regulates cancer cell metastasis, which in general involves cell detachment, migration, invasion, proliferation and angiogenesis. Recently, our laboratory identified a non-toxic, GAG-binding, cancer tissue targeting and cell penetrating peptide (CPPecp) derived from heparan sulfate binding domain of human eosinophil cationic protein (hECP). Fluorescein isothiocyanate (FITC)-labeled CPPecp bound to human lung epithelial, large celcancer cells (A549 and H460) and breast adenocarcinoma (MDA-MB-231) in a dose-dependent manner. Besides, in vitro assay employing Transwell® apparatus revealed that CPPecp inhibited migration and invasion of human lung (A549 and H460) and breast (MDA-MB-231) cancer cells. Practical applicate of our discovery to improve efficacy of anti-tumor liposomal drug, CPPecp was non-covalently mixed with an anti-tumor liposomal drug. This complex showed higher cytotoxicity toward A549 cells as compared with liposomal drug alone, and CPPecp did not stimulate drug leakage from liposome. In addition, covalent linkage of amine group CPPecp to NHS-modified phospholipid was carried out employing chemical synthesis. Molecular weight determination of CPPecp conjugated phospholipid was performed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). CPPecp-phospholipid conjugate will be integrated to liposomal drug. It will lead to further development of novel tumor targeting and cell penetrating peptide-based liposomal drug delivery system in the near future. In conclusion, CPPecp not only inhibits cancer cell migration and invasion but also improves efficacy of liposomal drug toward cancer cells, which in turn may facilitate development of a novel cell penetrating peptide-based biomaterial for epithelial tumor targeting.