Cancer-cell death induced by intracellular molecular self-assembly of synthesized organic molecules

2014 Fiscal Year Final Research Report

• Project/Area Number: 25630380
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biofunction/Bioprocess
• Research Institution: Kobe University
• Principal Investigator: TATSUO Maruyama 神戸大学, 工学(系)研究科(研究院), 准教授 (30346811)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 自己組織化 / ナノファイバー / 細胞内送達 / ガン細胞 / 選択的殺傷 / ペプチド

Outline of Final Research Achievements

We report cancer cell death initiated by the intracellular molecular self-assembly of a peptide lipid, which served as a gelator precursor. The gelator precursor was designed to form nanofibres via molecular self-assembly, after cleavage by a cancer-related enzyme (matrix metalloproteinase-7, MMP-7), leading to hydrogelation. The precursor exhibited remarkable cytotoxicity to 5 different cancer cell lines, while it exhibited low cytotoxicity to normal cells that secreted small amounts of MMP-7. Cancer cells secrete excessive amounts of MMP-7, which converted the precursor into a supramolecular gelator prior to its uptake by the cells. Once inside the cells, the supramolecular gelator formed a gel via molecular self-assembly, exerting stress upon the cancer cells. The present study thus describes a new drug where molecular self-assembly acts as the mechanism of cytotoxicity.

Free Research Field

生物化学工学