Article

Preparation of sodium deoxycholate (DOC) conjugated heparin derivatives for inhibition of angiogenesis and cancer cell growth.

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.
Bioconjugate Chemistry (Impact Factor: 4.58). 08/2008; 19(7):1346-51. DOI:10.1021/bc800173m
Source: PubMed

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.

0 0
 · 
0 Bookmarks
 · 
204 Views
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Numerous papers on heparin nanoparticles have been reported regarding targeting therapy and biomedical imaging. Here, we have summarized the prospects and opportunities of heparin as a carrier for cancer targeting and imaging. First, we proposed heparin-anticancer drug conjugates showing higher anticancer activity than free drug. The conjugated heparin (heparin-deoxycholate sodium) retained its ability to bind with angiogenic factors, showing a significant decrease in endothelial tubular formation. Second, targeting ligands conjugated heparin derivatives have introduced for a receptor mediated delivery of anticancer drug. Heparin-folic acid-retinoic acid (HFR) bioconjugates for treating cancer cells showed 3 fold higher efficacy than heparin-retinoic acid (HR). Besides active and passive targeting drug delivery, several papers have been reported regarding delivery of imaging agents by heparin nanoparticles. Finally, this research highlight has covered imaging agents such as gold nanoparticles and quantum dots (QDs) for noninvasive biomedical imaging. Very recently our group demonstrated that semiconductor QDs loaded heparin nanoparticles could also be administered through orally for noninvasive imaging. Due to promising features of heparin such as less toxic polysaccharide and easier modification, it was considered as a potent carrier for imaging agent and drug delivery.
    Quantitative imaging in medicine and surgery. 09/2012; 2(3):219-26.
  • [show abstract] [hide abstract]
    ABSTRACT: A case of an inferior vena cava (IVC) graft-enteric fistula manifesting with recurrent sepsis 11 years after a right hepatectomy extending to segments I and IV, the extrahepatic bile duct, and IVC followed by chemotherapy and external-beam radiation therapy is described. A preoperative workup revealed graft thrombosis with air bubbles inside the lumen. Laparotomy found a chronic fistula between the graft and the enteric biliary loop. Removal of the graft without further vascular reconstruction, a take-down of the biliary loop, and a redo hepaticojejunostomy were performed successfully. The diagnostic challenges, possible etiology, and therapeutic implications of this case are discussed.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 01/2012; 55(1):226-9. · 3.52 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: In this study, three types of hybrid nanotubes (NTs), ie, oxidized multiwalled carbon NTs (COOH MWCNTs), heparin (Hep)-conjugated MWCNTs (Hep MWCNTs), and diblock copolymer polyglycolic acid (PGA)-co-heparin conjugated to MWCNTs (PGA MWCNTs), were synthesized with improved biocompatibility and drug-loading capacity. Hydrophilic Hep substituents on MWCNTs improved biocompatibility and acted as nucleus-sensitive segments on the CNT carrier, whereas the addition of PGA enhanced drug-loading capacity. In the PGA MWCNT system, the amphiphilic copolymer (PGA-Hep) formed micelles on the side walls of CNTs, as confirmed by electron microscopy. The PGA system encapsulated the hydrophobic drug with high efficiency compared to the COOH MWCNT and Hep MWCNT systems. This is because the drug was loaded onto the PGA MWCNTs through hydrophobic forces and onto the CNTs by π-π stacking interactions. Additionally, most of the current drug-carrier designs that target cancer cells release the drug in the lysosome or cytoplasm. However, nuclear-targeted drug release is expected to kill cancer cells more directly and efficiently. In our study, PGA MWCNT carriers effectively delivered the active anticancer drug doxorubicin into targeted nuclei. This study may provide an effective strategy for the development of carbon-based drug carriers for nuclear-targeted drug delivery.
    International Journal of Nanomedicine 01/2013; 8:4427-40. · 3.46 Impact Factor

Full-text

View
2 Downloads
Available from