Guo Yufeng, Xu Haixing, Li Yiping, Wu Fengzheng, Li Yixuan, Bao Yun, Yan Xiumei, Huang Zhijun, Xu Peihu
Department of Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
J Biomater Appl. 2017 Jul;32(1):54-65. doi: 10.1177/0885328217712110. Epub 2017 May 29.
Graphene oxide (GO) modified with hyaluronic acid (HA) and Arg-gly-asp peptide (RGD) was designed as a dual-receptor targeting drug delivery system to enhance the specificity and efficiency of anticancer drug delivery. Firstly, GO-HA-RGD conjugate was characterized to reveal its structure and morphology. Whereafter, doxorubicin (Dox) as a model drug was loaded on GO-HA-RGD carrier, which displayed a high loading rate (72.9%, GO:Dox (w/w) = 1:1), pH-response and sustained drug release behavior. Cytotoxicity experiments showed that GO-HA-RGD possessed excellent biocompatibility towards SKOV-3 and HOSEpiC cells. Additionally, the GO-HA-RGD/Dox had a stronger cytotoxicity for SKOV-3 cells than either GO-HA/Dox (single receptor) or GO/Dox (no receptor). Moreover, celluar uptake studies illustrated that GO-HA-RGD conjugate could be effectively taken up by SKOV-3 cells via a synergic effect of CD44-HA and integrin-RGD mediated endocytosis. Hence, GO-HA-RGD nanocarrier is able to be a promising platform for targeted cancer therapeutic.
用透明质酸（HA）和精氨酸-甘氨酸-天冬氨酸肽（RGD）修饰的氧化石墨烯（GO）被设计为一种双受体靶向给药系统，以提高抗癌药物递送的特异性和效率。首先，对GO-HA-RGD共轭物进行表征以揭示其结构和形态。此后，将阿霉素（Dox）作为模型药物负载在GO-HA-RGD载体上，该载体显示出高负载率（72.9%，GO:Dox（w/w）=1:1）、pH响应和持续药物释放行为。细胞毒性实验表明，GO-HA-RGD对SKOV-3和HOSEpiC细胞具有优异的生物相容性。此外，GO-HA-RGD/Dox对SKOV-3细胞的细胞毒性比GO-HA/Dox（单受体）或GO/Dox（无受体）更强。而且，细胞摄取研究表明，GO-HA-RGD共轭物可通过CD44-HA和整合素-RGD介导的内吞作用的协同效应被SKOV-3细胞有效摄取。因此，GO-HA-RGD纳米载体能够成为一种有前景的靶向癌症治疗平台。
