title: 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: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Gayong
authors: G
authors: Shim
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Ji-Young
authors: JY
authors: Kim
authors: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Jeonghoon
authors: J
authors: Han
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Seung Woo
authors: SW
authors: Chung
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Soondong
authors: S
authors: Lee
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: yrbyun@snu.ac.kr.
authors: Youngro
authors: Y
authors: Byun
authors: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ohyk@snu.ac.kr.
authors: Yu-Kyoung
authors: YK
authors: Oh
mesh_terms: D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D006108:Graphite / Q000008:administration & dosage* / Q000737:chemistry; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010084:Oxidation-Reduction; D013656:Taurocholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D006495:Heparin, Low-Molecular-Weight; C580866:LHT7 compound; D013656:Taurocholic Acid; D006108:Graphite; D004317:Doxorubicin
keywords: Anti-angiogenic anticancer low molecular weight heparin derivative; Anticancer effect; Dispersion stability; Doxorubicin; Reduced graphene oxide