The effect of ligand density on in vivo tumor targeting of nanographene oxide.

Abstract

Recently, the application of nanographene oxide (nGO) as a drug delivery system has significantly increased. But, the rational engineering of nGO surface to improve its in vivo targeting and biodistribution remains mostly unexplored. In this study, we have prepared folic acid conjugated Pluronic for non-covalent functionalization of nanographene oxide (nGO) sheets and active tumor targeting. To modulate the ligand density on the nGO surface, different ratios of folate conjugated Pluronic and unmodified Pluronic were combined and used for coating nGO sheets. The surface density of targeting ligand linearly increased as the relative amount of folate conjugated Pluronic was increased. The association of functionalized nGOs with folate receptor overexpressing human epithelial mouth carcinoma cells (KB cells) was evaluated by flow cytometry. Cellular uptake of nGO by KB cells increased steadily with the increase in ligand density. In contrast, the in vivo experiment in mouse xenograft model did not show the steady increase in tumor targeting by increasing ligand density. Upon intravenous administration into KB tumor-bearing mice, tumor accumulation of nGO did not show a significant targeting effect up to 25% of ligand coating density. However, a strong and similar tumor accumulation of nGO was observed for both 50% and 100% folate coatings. Thus, a significant difference in tumor accumulation of nGO was observed between the low folate density groups and high folate density groups, suggesting the existence of a critical ligand density for tumor targeting. The significant difference of tumor targeting of nGO depending on ligand density also resulted in the dramatic change in photothermal tumor ablation by the irradiation of NIR laser.

• Authors: Jong Hyun Lee, Abhishek Sahu, Cheol Jang, Giyoong Tae
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 209 Pg. 219-28 (Jul 10 2015) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25937319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Folic Acid Transporters
• Ligands
• Oxides
• Poloxamer
• Graphite
• Folic Acid

Topics

• Animals
• Folic Acid (administration & dosage, chemistry, pharmacokinetics, pharmacology)
• Folic Acid Transporters (metabolism)
• Graphite (administration & dosage, chemistry, pharmacokinetics)
• Humans
• KB Cells
• Laser Therapy
• Ligands
• MCF-7 Cells
• Male
• Mice
• Mice, Nude
• NIH 3T3 Cells
• Nanostructures (administration & dosage, chemistry)
• Neoplasms (metabolism, pathology, therapy)
• Oxides (administration & dosage, chemistry, pharmacokinetics)
• Phototherapy
• Poloxamer (chemistry)
• Tumor Burden (drug effects)