Development of novel multifunctional nanoparticles based on uptake mechanism of endogenous albumin by pancreatic cancer cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02587
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: The University of Tokushima
• Principal Investigator: ISHIMA Yu 徳島大学, 大学院医歯薬学研究部(薬学域), 准教授 (00457590)
• Co-Investigator(Kenkyū-buntansha): 石田 竜弘 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (50325271) ; 小田切 優樹 崇城大学, 薬学部, 特任教授 (80120145)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: アルブミン / 膵臓がん

Outline of Final Research Achievements

Many nano antitumor drugs were developed based on the enhanced permeability and retention (EPR) effect. However, these EPR effect-based therapeutic systems a less effective in malignant tumors with low vascular permeability, such as pancreatic tumors. Since the EPR effect depends on nanoparticles' size, we first determined nanoparticles' size associating with a high tumor-targeting rate in a human pancreatic tumor xenograft model with low vascular permeability. The tumor-targeted delivery and antitumor activity of PTX loaded albumin nanoparticles were significantly improved by optimizing the mean nanoparticle diameter to 30 nm. Furthermore, the nitric oxide-PTX loaded 30 nm-albumin nanoparticles treatment on model mice achieved a significantly higher survival rate than conventional therapy. These findings suggest that 30 nm-albumin nanoparticles have a high therapeutic effect against human pancreatic tumors.

Free Research Field

薬剤学、薬物送達学

Academic Significance and Societal Importance of the Research Achievements

本研究は、治療満足度の低い膵臓がんを対象としたものであり、膵臓がんへの特異的デリバリーを可能にするキャリアの開発に成功した。このキャリアは人の体に従来から存在するアルブミンを原料としていることから、免疫原性や副反応も少ない安全なものであり、アルブミンの様々な薬物を結合する特性から、複数種類の抗がん剤の搭載も可能である。臨床応用されることで、現状の膵臓がんの治療満足度の改善が見込められ、学術的意義のみならず、社会的意義も大きいと考えている。