title: Dual-targeting delivery system for bone cancer: synthesis and preliminary biological evaluation.
abstract: Chemotherapy in treatment of malignant tumors has many side effects due to the poor physiochemical properties and the toxicity to normal tissues. The dual-targeting drug delivery system combining two high-affinity ligands can target anticancer drug primary to the diseased tissue, then to the tumor, which provides both greater efficacy of treatment and less harm to normal tissues. In this paper, a novel dual-targeting moiety RGD(7) (R-G-D-D-D-D-D-D-D; Nonapeptide for bone cancer combining D(6) peptide as bone target moiety and RGD peptide as tumors target moiety was contracted. A series of bone and/or tumor targeting conjugates have been synthesized in a convergent approach and well characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The hydroxyapatite (HAP) binding, water solubility, the drug release and the distribution in vivo were evaluated. All the conjugates were water-soluble and able to release the parent drugs in vitro. The bone-targeting property of the dual-targeting delivery system was enhanced from the results of the HAP binding and the distribution in vivo. The experiment for verifying tumor targeting property was underway. These results provided an effective entry to the development of a new dual-targeting delivery system for bone cancer.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Junhan
authors.initials: J
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Dongsheng
authors.initials: D
authors.lastname: He
authors.forename: Junzhu
authors.initials: J
authors.lastname: Pan
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D017886:Durapatite / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D011355:Prodrugs / Q000138:chemical synthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D011355:Prodrugs; C047981:arginyl-glycyl-aspartic acid; D017886:Durapatite; D005472:Fluorouracil