S-Nitrosated human serum albumin dimer as novel nano EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes

2014 Fiscal Year Final Research Report

• Project/Area Number: 25860118
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kumamoto University
• Principal Investigator: ISHIMA Yu 熊本大学, 薬学部, 助教 (00457590)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ヒト血清アルブミン / 一酸化窒素 / 癌 / EPR効果 / ドキシル / アブラキサン

Outline of Final Research Achievements

The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors, and it can serve as a basis for the development of macromolecular anticancer therapy. We have previously found that recombinant human serum albumin dimer, and especially its S-nitrosated form (SNO-HSA-Dimer), is an enhancer of the EPR effect. In this study, we investigated the influence of SNO-HSA-Dimer on the anti-tumor effect of two types of macromolecular anti-tumor drugs. In mice having C26 tumors with highly permeable vasculature, SNO-HSA-Dimer increases tumor accumulation of the drugs by a factor 3-4 and thereby their anti-tumor effects. Furthermore, SNO-HSA-Dimer improves the anti-metastatic effects of Doxil and reduces its minor uptake in non-tumerous organs such as liver and kidney. The present findings indicate that SNO-HSA-Dimer is promising for enhancing the EPR effect and consequently the specific, therapeutic effects of macromolecular anticancer drugs.

Free Research Field

薬剤学