Heteromultivalent liposomal nanoconstructs for enhanced targeting and shear-stable binding to active platelets for site-selective vascular drug delivery

Biomaterials. 2011 Dec;32(35):9504-14. doi: 10.1016/j.biomaterials.2011.08.067. Epub 2011 Sep 8.


Activated platelets play multiple roles in vascular diseases. Hence, a delivery vehicle that can specifically target activated platelets and stay retained under a hemodynamic environment can potentially enhance the efficacy of vehicle-encapsulated vascular drug by protecting it from rapid plasma deactivation, reducing its systemic non-specific side-effects, and increasing its therapeutic index at disease sites undergoing platelet hyperactivity. We rationalized that liposomal nanoconstructs surface-modified with two kinds of peptide that simultaneously bind integrin α(IIb)β(3) and P-selectin on activated platelets can provide synergistic mechanisms for enhanced selectivity to vascular disease sites. We further hypothesized that dual-receptor targeting will enhance binding strength and retention under flow. We tested this using fluorescently-labeled liposomes, surface-modified by an RGD peptide targeted to active α(IIb)β(3) and an EWVDV peptide targeted to P-selectin. The liposomes were studied for their platelet-specific interactions inside a parallel plate flow chamber at low-to-high shear stresses. The interaction specificity was further confirmed by flow cytometry. Our results indicate that liposomes surface-modified with both RGD and EWVDV simultaneously have higher selectivity as well as retention to activated platelets under flow compared to liposomes bearing any one peptide type. These results establish the potential of our nanoconstructs for enhanced site-selective drug delivery in vascular diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Blood Vessels / drug effects
  • Blood Vessels / metabolism*
  • Drug Delivery Systems / methods*
  • Flow Cytometry
  • Humans
  • Ligands
  • Liposomes / chemistry*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Nanostructures / chemistry*
  • Oligopeptides / pharmacology
  • Platelet Activation* / drug effects
  • Protein Binding / drug effects
  • Receptors, Cell Surface / metabolism


  • Ligands
  • Liposomes
  • Oligopeptides
  • Receptors, Cell Surface
  • arginyl-glycyl-aspartic acid