Induction of EPR effects on microtumors by combretastatin and its microcirculation mechanism

2014 Fiscal Year Final Research Report

• Project/Area Number: 24650643
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: Tohoku University
• Principal Investigator: HORI Katsuyoshi 東北大学, 加齢医学研究所, 准教授 (00143032)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 腫瘍血流遮断 / コンブレタスタチン / 腫瘍血管 / EPR効果 / 高分子ミセル / DDS / インターフェイス

Outline of Final Research Achievements

Nanoparticles are difficult to extravasate from initial stage tumor vessels. Therefore, enhanced-permeability and retention (EPR) effects do not occur in such vessels. A combretastatin derivative, Cderiv, enhances vascular permeability. To elucidate the microcirculation mechanisms of the EPR effect, we investigated the structure and function of tumor vessels and tumor-host interface (T-HI) vessels after Cderiv administration. We also assessed the therapeutic enhancement effects of the combination of doxorubicin micelle with Cderiv. Results show the following. (1) The T-HI vessel endothelium contained many vesiculo-vacuolar organelles (VVO), which contribute to macromolecule extravasation, even after the Cderiv administration. (2) Combination therapy (Cderiv + doxorubicin micelle) markedly inhibited LY80 tumor growth. The presence of VVO and the decline of tumor microcirculation function involving T-HI are important for the EPR effect.

Free Research Field

実験腫瘍学