Dysfunctional endothelium contributes to more disease than any other tissue in the body. MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) have the potential to help study and treat endothelial cells in vivo by durably silencing multiple genes simultaneously, but efficient RNA delivery has so far remained challenging. Our polymeric nanoparticles discovered at M.I.T made of low molecular weight polyamines and lipids can deliver these RNAs to endothelial cells with high efficiency, thereby facilitating the simultaneous modification of expression of multiple endothelial genes in vivo.