title: Preparation of sodium deoxycholate (DOC) conjugated heparin derivatives for inhibition of angiogenesis and cancer cell growth.
abstract: We describe new DOC (sodium deoxycholate)-heparin nanoparticles for in vivo tumor targeting and inhibition of angiogenesis based on chemical conjugation and the enhanced permeability and retention (EPR) effect. Heparin has been used as a potent anticoagulant agent for 70 years, and has recently been found to inhibit the activity of growth factors which stimulate the smooth muscle cells around tumor. From the results, DOC and heparin were conjugated by bonding carboxyl groups of heparin with amine groups of aminated sodium deoxycholate. Larger antitumor effects of the DOC-heparin VI (8.5 mol of DOC coupled with 1.0 mol heparin) were achieved in animal studies, compared to heparin alone. We confirmed that the conjugated heparin retained its ability to inhibit binding with angiogenic factor, showing a significant decrease in endothelial tubular formation. These results provide new insights into the nontoxic anticancer drug carrier as well as the design of multifunctional bioconjugates for targeted drug delivery.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, The Catholic University of Korea, College of Medicine Uijeongbu, St. Mary's Hospital, Kyunggi-Do 480-717, Korea.
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Cho
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Moon
authors.forename: Go-Eun
authors.initials: GE
authors.lastname: Park
authors.forename: Ok Chul
authors.initials: OC
authors.lastname: Jeon
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.forename: Yong-Kyu
authors.initials: YK
authors.lastname: Lee
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003840:Deoxycholic Acid / Q000737:chemistry* / Q000494:pharmacology*; D005029:Ethylenediamines / Q000737:chemistry; D065427:Factor Xa Inhibitors; D005260:Female; D005561:Formates / Q000737:chemistry; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D000925:Anticoagulants; D000970:Antineoplastic Agents; D005029:Ethylenediamines; D065427:Factor Xa Inhibitors; D005561:Formates; D003840:Deoxycholic Acid; D006493:Heparin