Multiple Blockades of the HGF/Met Signaling Pathway for Metastasis Suppression Using Nanoinhibitors.

The hepatocyte growth factor (HGF)/HGF receptor (Met) signaling pathway serves as a potential target for preventing tumor metastasis yet poorly explored. Here, we developed a Met-targeted nanoinhibitor to efficiently suppress metastasis via a multiple blockading HGF/Met signaling pathway. A biocompatible nanovector comprising multiple type of inhibitors enables interrupting extracellular domain dimerization and intracellular domain phosphorylation simultaneously. Such a comprehensive blockade of signaling pathway restrains unregulated tumor cell migration, invasion, and proliferation and thus remarkably suppresses metastasis in an orthotopic breast tumor model. This method provides a safe and effective option for metastasis inhibition via modulation of the cell signaling pathway. To our best knowledge, the strategy of the multiple blockading signaling pathway has not been reported for preventing tumor metastasis.