Development of molecular targeted anticancer drug using peptide probe for glioblastoma multiforme

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10330
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Shiino Akihiko 滋賀医科大学, 神経難病研究センター, 准教授 (50215935)
• Co-Investigator(Kenkyū-buntansha): 谷垣 健二 滋賀県立成人病センター(研究所), 神経病態研究部門, 専門研究員 (70362473) ; Zhao Li 滋賀医科大学, 医学部, 客員研究員 (40636156)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 悪性神経膠腫 / 分子標的薬 / 血液脳関門 / ファージディスプレイ / DDS / がん幹細胞 / エンドゾーム / MRI

Outline of Final Research Achievements

We try to develop a molecular targeted anti-cancer drug for glioblastoma, which is the most malignant and difficult for treatment. In the brain, tumor cells are protected by blood brain barrier (BBB) that inhibiting transmission of anti-cancer drugs. First, we developed a peptide probe by a method of phage display, which selectively entered into tumor cells and could pass-through BBB in vivo. The proto-type of anti-cancer agent of ours was made by simply conjugated an anticancer drug to the peptide probe, which did not show any effect to the cancer cells. Possible mechanism of this would be that the tumor cells must discharge or break down the agent via endocytosis-endosome mechanism. To overcome, we added pH-dependent membrane active peptide (PMAPs) to the molecular targeted anti-cancer drug and confirmed the effect of tumor shrinkage in PDX model mouse on MRI.

Free Research Field

脳神経外科学