Drug Design for Hypoxic Theranostics

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H02863
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Aoyama Gakuin University
• Principal Investigator: Tanabe Kazuhito 青山学院大学, 理工学部, 教授 (40346086)
• Co-Investigator(Kenkyū-buntansha): 西原 達哉 青山学院大学, 理工学部, 助教 (00773201)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 低酸素細胞 / 人工核酸 / 放射線照射 / 還元酵素

Outline of Final Research Achievements

Hypoxic cells generate within solid tumors and are known to be resistant to radiotherapy and to cause malignant of cancer. In this study, we developed artificial nucleic acids that could be the next generation of hypoxia therapeutics and diagnostics, and advanced molecular design that could realize theranostics for hypoxic cells. We synthesized artificial nucleic acids whose functional groups are converted by X-ray irradiation under hypoxic conditions and express their original functions. We also prepared artificial nucleic acids that show selective accumulation ability in hypoxic cells by functional group modification. Both nucleic acids showed good performance and were found to be driven under hypoxic conditions.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究では低酸素セラノスティックを実現しうる人工核酸型分子システムを開発した。具体的には2種類のシステムの開発に成功し、いずれも低酸素条件下で駆動した。核酸は遺伝子の担い手であるが、化学修飾を加えることによって多機能性を示す。すなわち、薬剤を導入したり、蛍光色素やMRI活性な元素を導入することによって治療薬・診断薬になり得る。全て申請者のオリジナルな技術を用いて作成する本システムは、低酸素細胞の診断と治療に確実な進歩をもたらすと考えられる。