Treatment of hepatocellular carcinoma with autologous platelets encapsulating sorafenib or lenvatinib: A novel therapy exploiting tumor-platelet interactions.

Abstract

Hepatocellular carcinoma (HCC) activates platelets through the action of adjacent sinusoidal cells. 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 multiple 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). The therapeutic effect was then analyzed by ultrasonography (US) and histopathological analysis. Histopathological and US analysis demonstrated extensive tumor necrosis in the tumor tissue of SOR-PLT or LEN-PLT, but not in other experimental groups. By liquid chromatography-mass spectrometry, more abundant sorafenib was detected in tumor tissues after SOR-PLT administration than in surrounding normal tissues, but no such difference in sorafenib level was observed with SOR administration. Therefore, the use of autologous platelets encapsulating drugs might be a novel therapeutic strategy for HCC.

• Authors: Hiroki Tanaka, Kie Horioka, Takumu Hasebe, Koji Sawada, Shunsuke Nakajima, Hiroaki Konishi, Shotaro Isozaki, Masanori Goto, Yumiko Fujii, Yuki Kamikokura, Katsuhiro Ogawa, Yuji Nishikawa
• Journal: International journal of cancer (Int J Cancer) Vol. 150 Issue 10 Pg. 1640-1653 (05 15 2022) ISSN: 1097-0215 [Electronic] United States
• PMID: 34935134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 UICC.

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Quinolines
• Sorafenib
• lenvatinib

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Endothelial Cells (pathology)
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Phenylurea Compounds (pharmacology, therapeutic use)
• Quinolines (pharmacology, therapeutic use)
• Rats
• Sorafenib (pharmacology, therapeutic use)