Basic research for development of the DDS system considering tissue and intracellular drug distribution

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15600
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: NISHIDA TOSHIROU 国立研究開発法人国立がん研究センター, 中央病院, 病院長 (40263264)
• Co-Investigator(Kenkyū-buntansha): 安永 正浩 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (80450576)
• Research Collaborator: KUROKAWA Kazuo 理化学研究所, 光量子工学研究領域 (40333504) ; MANABE Shino 理化学研究所, 伊藤細胞制御化学研究室 (60300901)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Drug-Delivery System / 分子標的治療薬 / イマチニブ / 消化管間質腫瘍 / 細胞株

Outline of Final Research Achievements

It is important to develop DDS which efficiently and specifically delivers anti-cancer agents to cancer cells. The purpose of this research is to develop basic technology to measure accurately drug distribution at cellular and organellar levels using GIST-imatinib as a model. We have studied using xenograft model and GIST cell lines. Imatinib distribution in tumor tissues was measured with mass-microscopes whose sensitivity was enhanced nearly 10-hold.
Although tumor vascular density greatly decreased after imatinib therapy, there was no change in tumor tissue distribution of imatinib in xenograft models. Intracellular imatinib distribution was measured by fluorescent-tagged imatinib, Turn-ON method, and using anti-imatinib antibody. When imatinib entered into tumor cells, it rapidly accumulated mainly in the secondary lysosome, and partly distributed ER-like structures. Taken together, imatinib was accumulated mainly in lysosome and partly in ER-like structures of tumor cells.

Free Research Field

外科学一般