The surface of mesoporous silica nanoparticles (MSNs) has been modified for enhancing their cellular uptake, cell targeting, bioimaging, and controlled drug release. For this purpose, covalent anchorage on the silica surface was predominantly exploited with a wide range of bioactive molecules. Here, we describe a facile self-assembly method to prepare a hybrid peptide silica system composed of octyl-modified mesoporous silica nanoparticles (MSNs) and peptide amphiphiles (PAs). The hydrophobic organosilane surface of mesoporous silica was coated with amphiphilic peptide molecules. The peptide functionalized particles exhibited good cyto-compatibility with vascular smooth muscle and vascular endothelial cells. The peptide coating also improved the cellular uptake of particles up to 6.3 fold, which is promising for the development of highly efficient MSN based theranostic agents. © 2014 the Partner Organisations.