DDS using autologous platelets: a new therapeutic strategy to reverse the hepatocarcinoma-platelet interaction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Tanaka Hiroki 旭川医科大学, 医学部, 講師 (70596155)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肝がん / 血小板

Outline of Final Research Achievements

Activated platelets bind to tumor-associated endothelial cells and release growth factors that promote tumor progression. We hypothesized that platelets encapsulated with tumor inhibitors would function as drug carriers for tumor therapy. We propose a therapeutic strategy for HCC using autologous platelets encapsulating tyrosine kinase inhibitors in a rat chemically induced HCC model. Sorafenib or lenvatinib was encapsulated in platelets isolated from tumor-bearing rats in vitro. The rats were divided into groups that received repeated intravenous injections (twice a week for 10 weeks) of the following materials: placebo, sorafenib (SOR), lenvatinib (LEN), autologous platelets, autologous platelets encapsulating sorafenib (SOR-PLT) and autologous platelets encapsulating lenvatinib (LEN-PLT). We observed extensive tumor necrosis in the tumor tissue of SOR-PLT or LEN-PLT. Therefore, the use of autologous platelets encapsulating drugs might be a novel therapeutic strategy for HCC.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

ソラフェニブの臨床応用により、肝細胞癌に対する全身化学療法の使用成績が大きく変化した。最近、レンバチニブもソラフェニブの治療効果を上回る目的で使用されている。しかし、これらの分子標的治療薬による副作用の報告が多く、副作用の少ない治療が望まれている。本研究では、肝細胞癌と血小板の強い相互作用を利用することで、自己血小板を薬物キャリアとして使用し、ラット肝細胞癌モデルにおいて、腫瘍組織に効率的に薬物を送達できることを実証した。この戦略は肝細胞癌の治療に大きな影響を与えると期待できる。