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Targeting liver sinusoidal endothelial cells with mi R ‐20a‐loaded nanoparticles reduces murine colon cancer metastasis to the liver
Author(s) -
Marquez Joana,
FernandezPiñeiro Ines,
AraúzoBravo Marcos J.,
Poschmann Gereon,
Stühler Kai,
Khatib AbdelMajid,
Sanchez Alejandro,
Unda Fernando,
Ibarretxe Gaskon,
Bernales Irantzu,
Badiola Iker
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31343
Subject(s) - downregulation and upregulation , metastasis , cancer research , microrna , in vivo , biology , liver cancer , microbiology and biotechnology , cancer , chemistry , hepatocellular carcinoma , biochemistry , gene , genetics
Phenotypic transformation of liver sinusoidal endothelial cells is one of the most important stages of liver metastasis progression. The miRNA effects on liver sinusoidal endothelial cells during liver metastasis have not yet been studied. Herein, whole genome analysis of miRNA expression in these cells during colorectal liver metastasis revealed repressed expression of microRNA‐20a. Importantly, downregulation of miR‐20a occurs in parallel with upregulation of its known protein targets. To restore normal miR‐20a levels in liver sinusoidal endothelial cells, we developed chondroitin sulfate‐sorbitan ester nanoparticles conjugated with miR‐20a in a delivery system that specifically targets liver sinusoidal endothelial cells. The restoration of normal mir‐20a levels in these cells induced downregulation of the expression of its protein targets, and this also resulted in a reduction of in vitro LSEC migration and a reduction of in vivo activation and tumor‐infiltrating capacity and ability of the tumor decreased by ∼80% in a murine liver metastasis model.