Preparation of sodium deoxycholate (DOC) conjugated heparin derivatives for inhibition of angiogenesis and cancer cell growth.
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.
Cho
Kwang Jae
KJ
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.
Moon
Hyun Tae
HT
Park
Go-Eun
GE
Jeon
Ok Chul
OC
Byun
Youngro
Y
Lee
Yong-Kyu
YK
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*
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