Manipulation of dynamic tumor blood vessel permeability: nano-eruption

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06627
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: Inoue Yuta 東京大学, 医学部附属病院, 登録研究員 (10802358)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Keywords: 癌

Outline of Final Research Achievements

We have recently discovered dynamic extravasation through transient tumor vascular bursts. This phenomenon, named as nano-eruption (NE), increases accumulation of larger nanomicelles in tumors. To unveil the mechanisms and ultimately control NE, conditions that either provoke or inhibit NE is under investigation. Tumor-bearing mice were treated with either TGF-β inhibitor and chloroquine. The 30- or 70- nm fluorescent-labeled micelles were administered, and their tumor distribution was assessed over time with intravital microscopy. TGF-β inhibitor increased the frequency, maximum area & velocity and duration time of NE. Chloroquine did not affect the frequency, but increased the maximum area & velocity and duration time of NE. Our result demonstrated that different modulator drugs enhanced the different aspect of the NE, and the consequences are also dependent on the micelle size.

Free Research Field

ドラッグデリバリーシステム

Academic Significance and Societal Importance of the Research Achievements

Nano eruptionは2016年に初めて報告された。この腫瘍血管が一過性に破綻し高分子ナノミセル薬剤が腫瘍組織へ噴出する動的透過経路を利用して新たなドラッグデリバリーシステムを構築できればこれまでにないがん治療の選択肢となりうる。そのためにはNano eruptionの機序解明と制御が必要だが、本研究でNano eruptionの発生変化を明らかにすることはその第一歩となる。また、これまで薬剤併用によるNano eruptionの変化は報告されていないので本研究の論文化は学術的分野からの関心も高いと思われる。