title: Graphene-based anticancer nanosystem and its biosafety evaluation using a zebrafish model.
abstract: In this paper, a facile strategy to develop graphene-based delivery nanosystems for effective drug loading and sustained drug release was proposed and validated. Specifically, biocompatible naphthalene-terminated PEG (NP) and anticancer drugs (curcumin or doxorubicin (DOX)) were simultaneously integrated onto oxidized graphene (GO), leading to self-assembled, nanosized complexes. It was found that the oxidation degree of GO had a significant impact on the drug-loading efficiency and the structural stability of nanosystems. Interestingly, the nanoassemblies resulted in more effective cellular entry of DOX in comparison with free DOX or DOX-loaded PEG-polyester micelles at equivalent DOX dose, as demonstrated by confocal microscopy studies. Moreover, the nanoassemblies not only exhibited a sustained drug release pattern without an initial burst release, but also significantly improved the stability of formulations which were resistant to drug leaking even in the presence of strong surfactants such as aromatic sodium benzenesulfonate (SBen) and aliphatic sodium dodecylsulfonate (SDS). In addition, the nanoassemblies without DOX loading showed negligible in vitro cytotoxicity, whereas DOX-loaded counterparts led to considerable toxicity against HeLa cells. The DOX-mediated cytotoxicity of the graphene-based formulation was around 20 folds lower than that of free DOX, most likely due to the slow DOX release from complexes. A zebrafish model was established to assess the in vivo safety profile of curcumin-loaded nanosystems. The results showed they were able to excrete from the zebrafish body rapidly and had nearly no influence on the zebrafish upgrowth. Those encouraging results may prompt the advance of graphene-based nanotherapeutics for biomedical applications.
authors.affiliation: Key Laboratory of Biomedical Polymers (The Ministry of Education), Department of Chemistry, Wuhan University, Wuhan, China.
authors.forename: Chen-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Xiong
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Jia
authors.forename: Xu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Cheng
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Sun
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006108:Graphite / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008823:Micelles; D049329:Nanostructures; D009369:Neoplasms / Q000188:drug therapy; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D006108:Graphite; D004317:Doxorubicin; D003474:Curcumin