Construction of a method for enhancing the tumor accumulation of liposomes via improving tumor microenvironment focusing on macrophages

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06524
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Kono Yusuke 神戸薬科大学, 薬学部, 講師 (60732823)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腫瘍内マクロファージ / リポソーム / 腫瘍内血管

Outline of Final Research Achievements

In this study, I aimed to enhance the tumor accumulation and anti-tumor efficacy of anti-cancer drug-loaded liposomes by improving tumor microenvironment through the phenotypic conversion of tumor-infiltrated macrophages using disulfiram. In addition, I also tried to construct the diagnosis for predicting the therapeutic effect of liposomes combined with disulfiram. The tumor accumulation and anti-tumor efficacy of doxorubicin-loaded liposomes were significantly increased by disulfiram-induced phenotypic conversion of macrophages from M2 to M1 in both CT26 and B16/BL6 solid tumor. In addition, it is likely that the increasing ratio of anti-tumor efficacy by disulfiram may be correlated with the number of pericytes in CT26 tumor and vascular endothelial cells in B16/BL6 tumor, respectively.

Free Research Field

薬物送達学

Academic Significance and Societal Importance of the Research Achievements

本研究で構築したマクロファージの極性を転換する手法は、血管新生の抑制のみでなく壁細胞による血管安定化も誘導でき、従来のVEGFを阻害する手法よりも効率的に血管の構造・機能を正常化することが可能である。本手法を利用してリポソームの腫瘍移行性を向上するアプローチを臨床において構築できれば、微粒子性抗がん剤の治療効果向上と適応拡大につながる。
また、リポソーム製剤のがん治療効果を予測するためのマーカー候補の探索は、効果が得られる患者を適切に選別するための予測法の構築につながり、これにより効果の期待できない患者への不要な抗がん剤投与による副作用の発現や医療費の負担を回避できる。