Manipulation of dynamic tumor blood vessel permeability: nano-eruption

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16766
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Inoue Yuta 東京大学, 医学部附属病院, 届出研究員 (10802358)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 癌 / ナノメディシン

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 腫瘍血管系の一時的で不規則な開口部（dynamic vent）を介してドラッグデリバリーシステム（DDS）が腫瘍組織に送達する動的な血管透過性亢進現象である。Nano-eruptionの制御はDDSの効率を改善することが期待される。本研究からTGF-β阻害薬とクロロキンとナノメディシンのサイズを介したNano-eruptionの制御は、DDSの効率をさらに促進することが示唆された。