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.