Development of photodynamic therapy probes for cancer with single cell resolution and their evaluation with clinical samples

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H02606
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: Urano Yasuteru 東京大学, 大学院薬学系研究科(薬学部), 教授 (20292956)
• Co-Investigator(Kenkyū-buntansha): 神谷 真子 東京大学, 大学院医学系研究科(医学部), 講師 (90596462)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 細胞殺傷 / がん / 光線力学療法 / ケミカルバイオロジー / 単一細胞 / activatable増感プローブ

Outline of Final Research Achievements

Based on the molecular design strategies of fluorogenic probes capable of detecting target cells with single-cell level resolution, which have been established by this group with using the concept of intramolecular spirocyclization and quinone methide intermediate, we succeeded to develop novel photo-sensitizing probes for ablating beta-galactosidase expressing cells in a single-cell resolution manner. It was also capable to ablate lacZ-positive cells selectively by applying the probe to co-culture of lacZ-positive and negative cells, which could not be realized by so far developed photo-sensitizing probes without forming quinone methide intermediate.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

本研究課題の遂行の結果開発された、これまでの小分子プローブでは達成できなかった一細胞レベル空間分解能での細胞光殺傷を可能とさせる光増感プローブは、極めて高い選択性での疾患治療、特にがんの局所治療を可能とさせる画期的な技術であり、代表者が現在も精力的に行っている、がん細胞を特徴付ける様々な酵素活性の探索研究結果と合わせることで、副作用の極めて少ない新たながん治療技術が誕生することが大いに期待される。