Multifunctional nanocomposite based on graphene oxide for in vitro hepatocarcinoma diagnosis and treatment
Multifunctional nanocomposite based on graphene oxide for in vitro hepatocarcinoma diagnosis and treatment
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基于氧化石墨烯的多功能纳米复合材料用于肝癌体外诊断和治疗
DOI：
10.1002/jbm.a.34148
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发表时间：
2012-09-01
影响因子：
4.9
通讯作者：
Li, Yong-Yong
中科院分区：
文献类型：
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作者：
Shen, Ai-Jun;Li, Dong-Liang;Li, Yong-Yong
由于其独特的化学和物理性质，氧化石墨烯（GO）在过去几年中吸引了大量研究人员探索其生物医学应用。本文合成了一种新型的基于GO的多功能纳米复合材料，并系统地研究了其在体外肝癌诊断和治疗中的应用。以钆-二乙烯三胺-五乙酸-聚（二烯丙基二甲基铵）氯化物（Gd-DTPA-PDDA）为磁共振成像（MRI）探针，通过简单的物理吸附对GO进行修饰，Gd 3+的负载效率高达0.314 mg mg-1。为了提高其肿瘤靶向成像和治疗效率，将所得中间产物进一步用叶酸（FA）修饰。最后，纳米复合物被允许负载抗癌药物盐酸阿霉素通过PP堆积和疏水相互作用，负载容量达到1.38 mg mg-1。MRI结果显示GO-PEG-FA/Gd/DOX的肿瘤靶向成像效率优于游离Gd 3+。在肿瘤相关条件下（pH 5.5），阿霉素从纳米复合材料中的体外释放在初始10 h快速，然后变得相对缓慢。此外，我们的实验表明，多功能纳米复合材料具有明显的细胞毒作用的癌细胞。以上结果为下一步的体内实验奠定了基础，并为恶性肿瘤的早期诊断和特异性治疗提供了可能。(c)2012 Wiley Periodicals，Inc. J Biomed Mater Res Part A：100A：24992506，2012.
Because of its unique chemical and physical properties, graphene oxide (GO) has attracted a large number of researchers to explore its biomedical applications in the past few years. Here, we synthesized a novel multifunctional nanocomposite based on GO and systemically investigated its applications for in vitro hepatocarcinoma diagnosis and treatment. This multifunctional nanocomposite named GO-PEG-FA/Gd/DOX was obtained as the following procedures: gadolinium-diethylenetriamine-pentaacetic acid-poly(diallyl dimethylammonium) chloride (Gd-DTPA-PDDA) as magnetic resonance imaging (MRI) probe was applied to modify GO by simple physical sorption with a loading efficiency of Gd3+ up to 0.314 mg mg-1. In order to improve its tumor targeting imaging and treatment efficiency, the obtained intermediate product was further modified with folic acid (FA). Finally, the nanocomposite was allowed to load anticancer drug doxorubicin hydrochloride via pp stacking and hydrophobic interaction with the loading capacity reaching 1.38 mg mg-1. MRI test revealed that GO-PEG-FA/Gd/DOX exhibit superior tumor targeting imaging efficiency over free Gd3+. The in vitro release of DOX from the nanocomposite under tumor relevant condition (pH 5.5) was fast at the initial 10 h and then become relatively slow afterward. Moreover, we experimentally demonstrated that the multifunctional nanocomposite exhibited obviously cytotoxic effect upon cancer cells. Above results are promising for the next in vivo experiment and make it possible to be a potential candidate for malignancy early detection and specific treatment. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 24992506, 2012.