RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer

J Control Release. 2014 Dec 28;196:222-33. doi: 10.1016/j.jconrel.2014.10.012. Epub 2014 Oct 22.


Targeting αvβ3 integrin is particularly promising for the treatment of bone metastases by targeting integrin-rich tumor cells and by inhibiting integrin-involved bone metastases. In this work, a liposomal drug delivery system conjugated with cyclic arginine-glycine-aspartic acid-tyrosine-lysine peptide (cRGDyk) as αvβ3 integrin ligand was thus developed to improve therapeutic efficacy in a mice model of bone metastasis from prostate cancer. The resultant liposomes were characterized in terms of size, morphology, zeta potential, stability, drug encapsulation percentage and loading efficiency, and drug release. Compared with free cisplatin and cRGDyk-free liposomes, cRGDyk conjugated liposomes showed significantly higher cellular uptake and higher cytotoxicity of loaded cisplatin, as evidenced by in vitro cell experiments. In vivo results revealed that free cisplatin and free cRGDyk could relieve tumor-induced pain but had no contributions to tumor regression and overall survival improvement. cRGDyk-free liposomal drug system with prolonged blood circulation time could accumulated in the tumor sites in the bone through enhanced permeability and retention (EPR) effects and however, did not exhibit desirable therapeutic efficacy superior to free cisplatin and free cRGDyk. This strongly suggested that ERP effects were not effective in treating metastases. By taking advantages of targeted drug delivery and synergistic antitumor activity of cRGDyk and loaded cisplatin, cRGDyk conjugated liposomal drug system could inhibit osteoclastic and osteoblastic bone lesions, relieve pain, and improve overall survival. Inspired by their enhanced therapeutic efficacy and low organ toxicity, cRGDyk conjugated liposomes could serve as an effective drug system for targeted and synergistic therapy of bone metastases.

Keywords: RGD peptide; bone metastasis; cisplatin; drug delivery; integrin; liposome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary*
  • Cell Line
  • Cisplatin / administration & dosage
  • Cisplatin / therapeutic use
  • Drug Delivery Systems / methods*
  • Humans
  • Infrared Rays
  • Liposomes / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides / administration & dosage*
  • Oligopeptides / chemistry
  • Oligopeptides / therapeutic use*
  • Pain / drug therapy
  • Pain / etiology
  • Particle Size
  • Prostatic Neoplasms / pathology*
  • Quantum Dots
  • Sulfides / chemistry
  • Survival Analysis


  • Antineoplastic Agents
  • Liposomes
  • Oligopeptides
  • Sulfides
  • arginyl-glycyl-aspartic acid
  • Cisplatin