To the best of our knowledge, the present study is the first in depth investigation from cell and molecular level of how low density lipoprotein receptor and neutrophils receptor co-mediated transportation of low bioavailability small-molecule drug brain-targeting nanocarrier correlate with their in vivo anti-ischemic stroke efficacy and protective mechanism on inflammatory response in ischemic stroke. This evidence concerns the gene VLDLR and ischemic stroke.