Reduced graphene oxide nanosheets coated with an anti-angiogenic anticancer low-molecular-weight heparin derivative for delivery of anticancer drugs.

Abstract

Here, we report reduced graphene oxide (rGO) nanosheets coated with an anti-angiogenic anticancer taurocholate derivative of low-molecular-weight heparin (LHT7) as a tumor-targeting nanodelivery platform for anticancer drugs. Surface coating of LHT7 onto rGO was confirmed using fluorescein isothiocyanate-labeled LHT7, monitored as fluorescence quenching due to associated rGO. Unlike plain rGO, LHT7-coated rGO (LHT-rGO) nanosheets maintained a stable dispersion under physiological conditions for at least 24h. Moreover, LHT-rGO provided greater loading capacity for doxorubicin (Dox) compared with uncoated rGO nanosheets. Following intravenous administration into KB tumor-bearing mice, in vivo tumor accumulation of LHT-rGO/Dox was 7-fold higher than that of rGO/Dox 24h post dosing. In tumor tissues, LHT-rGO/Dox was shown to localize not to the tumor vasculature, but rather to tumor cells. Intravenously administered LHT-rGO/Dox showed the greatest anti-tumor effect in KB-bearing mice, reducing tumor volume by 92.5%±3.1% compared to the untreated group 25days after tumor inoculation. TUNEL assays revealed that the population of apoptotic cells was highest in the group treated with LHT-rGO/Dox. Taken together, our results demonstrate that LHT-rGO nanosheets confer improved dispersion stability, tumor distribution and in vivo antitumor effects, and may be further developed as a potential active nanoplatform of various anticancer drugs.

• Authors: Gayong Shim, Ji-Young Kim, Jeonghoon Han, Seung Woo Chung, Soondong Lee, Youngro Byun, Yu-Kyoung Oh
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 189 Pg. 80-9 (Sep 10 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 24973719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Heparin, Low-Molecular-Weight
• LHT7 compound
• Taurocholic Acid
• Graphite
• Doxorubicin

Topics

• Adsorption
• Animals
• Antineoplastic Agents (administration & dosage, chemistry)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Doxorubicin (administration & dosage, chemistry)
• Drug Carriers (administration & dosage, chemistry)
• Drug Stability
• Female
• Graphite (administration & dosage, chemistry)
• Heparin, Low-Molecular-Weight (administration & dosage, analogs & derivatives, chemistry)
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• Nanostructures (administration & dosage, chemistry)
• Neoplasms (drug therapy, pathology)
• Oxidation-Reduction
• Taurocholic Acid (administration & dosage, analogs & derivatives, chemistry)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays