title: RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer.
abstract: 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.
authors.affiliation: Institute for Nautical Medicine, Nantong University, Nantong 226001, People's Republic of China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute for Nautical Medicine, Nantong University, Nantong 226001, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute for Nautical Medicine, Nantong University, Nantong 226001, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute for Nautical Medicine, Nantong University, Nantong 226001, People's Republic of China. Electronic address: chenzp@ntu.edu.cn.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Institute for Nautical Medicine, Nantong University, Nantong 226001, People's Republic of China. Electronic address: zhulizhou@ntu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002460:Cell Line; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007259:Infrared Rays; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010316:Particle Size; D011471:Prostatic Neoplasms / Q000473:pathology*; D045663:Quantum Dots; D013440:Sulfides / Q000737:chemistry; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009842:Oligopeptides; D013440:Sulfides; C047981:arginyl-glycyl-aspartic acid; D002945:Cisplatin
keywords: RGD peptide; bone metastasis; cisplatin; drug delivery; integrin; liposome