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

• Published in: International journal of cancer 2022-05, Vol.150 (10), p.1640-1653
• Main Authors: Tanaka, Hiroki, Horioka, Kie, Hasebe, Takumu, Sawada, Koji, Nakajima, Shunsuke, Konishi, Hiroaki, Isozaki, Shotaro, Goto, Masanori, Fujii, Yumiko, Kamikokura, Yuki, Ogawa, Katsuhiro, Nishikawa, Yuji
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Drug delivery; Endothelial cells; Endothelial Cells - pathology; Growth factors; Hepatocellular carcinoma; Humans; Intravenous administration; lenvatinib; Liquid chromatography; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Mass spectroscopy; Medical research; Medicin och hälsovetenskap; Phenylurea Compounds - pharmacology; Phenylurea Compounds - therapeutic use; platelet; Platelets; Protein-tyrosine kinase; Quinolines - pharmacology; Quinolines - therapeutic use; Rats; sorafenib; Sorafenib - pharmacology; Sorafenib - therapeutic use; Targeted cancer therapy
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.33915

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. What's new? Hepatocellular carcinoma activates platelets, which in turn bind to tumour‐associated endothelial cells and release growth factors that promote tumour progression. Here, the authors hypothesise that it may be possible to harness platelets as drug carriers for tumour therapy. Using a chemically‐induced hepatocellular carcinoma rat model, they demonstrate that autologous platelets encapsulating multiple tyrosine kinase inhibitors can be used to efficiently deliver the anticancer drugs to tumour tissues. The findings point to a novel potential therapeutic approach for hepatocellular carcinoma.