Nanoparticle Therapy Reduces Liver Metastasis Dramatically

Targeting sinusoidal endothelial cells with nanoparticles loaded with micro-RNA elements reduces colon cancer (CC) metastasis to the liver by 80%, according to a new study.

Researchers at the University of the Basque Country (UPV/EHU; Vizcaya, Spain) and the University of Santiago de Compostela (A Coruña, Spain) conducted a study in mice that was designed to examine if restoring the function of altered sinusoidal endothelial cells in the liver could help slow down the CC metastatic process in the liver, since it is known that damaged endothelial cells promote angiogenesis, helping the metastatic tumor mass to grow.

The researchers first induced liver metastasis in mice by using CC cells. From the resulting tumor mass they then extracted endothelial cells. When comparing these endothelial cells with healthy ones, they found that that both proteins and micro-RNA constituents were altered. Using biocomputing tools they then screened and selected the proteins and relevant micro-RNA elements, ending up with a specific micro-RNA, miR-20a, which appears in healthy endothelial cells, but disappears in cells in contact with the tumor.

To restore normal miR-20a levels, the researchers then developed chondroitin sulfate-sorbitan ester nanoparticles, which were conjugated with miR-20a in a delivery system that specifically targets liver sinusoidal endothelial cells. The restoration of normal mir-20a levels induced downregulation of the expression of its protein targets, resulting in a reduction of in vitro cell migration and a reduction of in vivo activation and tumor-infiltrating capacity and ability of the tumor by about 80%. The study was published on March 15, 2018, in the International Journal of Cancer.

“The pathological analysis revealed that, in the cases treated, far fewer new blood vessels had formed inside the tumors. If it is ever used as a treatment, it will be a complementary treatment,” said senior author Iker Badiola, PhD, of the UPV/EHU department of cell biology and histology. “You can't ignore the fact that the metastasis goes on growing 20% and, what is more, at no time are the tumor cells destroyed nor are they attacked directly. The strategy of tackling the metastasis that we have achieved involves limiting the supply of nutrients and oxygen; in other words, we restrict the help.”

Metastasis involves a complex series of steps in which cancer cells leave the original tumor site and migrate to other parts of the body via the bloodstream, via the lymphatic system, or by direct extension. To do so, malignant cells break away from the primary tumor by degrading the surrounding extracellular matrix (ECM), which separates the tumor from adjoining tissues, migrating to other organs. As one of the critical events required for subsequent tumor growth is blood supply, it is therefore thought that angiogenesis inhibitors could prevent or reduce the growth of metastases.

Related Links:
University of the Basque Country
University of Santiago de Compostela