Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, 117456, Republic of Singapore.
Int J Pharm. 2017 Dec 20;534(1-2):297-307. doi: 10.1016/j.ijpharm.2017.10.045. Epub 2017 Nov 5.
We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO-DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, α-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of α-amylase to simulate tumor conditions, GO-DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO. Under the same conditions, the cytotoxic effects of GO-DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO/DOX. Employing an in vitro biomimetic microfluidic blood vessel model lined with human umbilical vein endothelial cells, we evaluated the tumor vasculature endothelial permeation of GO-DEX and GO using dextrans of 10 and 70kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO-DEX and GO were 4.3- and 4.9-fold greater than that of 70kDa dextran and 2.7- and 3.1-fold higher than that of 10kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier.
我们合成了一种葡聚糖（DEX）接枝氧化石墨烯（GO）纳米载体（GO-DEX），作为一种潜在的药物传递系统，以响应肿瘤相关刺激物 - 淀粉酶，它具有高通透性，可以穿过有窗孔的内皮屏障到达肿瘤部位。在酸性 pH 值和存在α-淀粉酶以模拟肿瘤条件下，GO-DEX 释放的阿霉素（DOX）量比 GO 高 1.5 倍。在相同条件下，GO-DEX/DOX 的细胞毒性作用比游离 DOX 高 2 倍，比 GO/DOX 高 2.9 倍。我们使用 10 和 70kDa 的葡聚糖作为对照和标准，在体外仿生微流控血管模型中评估了 GO-DEX 和 GO 对人脐静脉内皮细胞的肿瘤血管内皮通透性。结果表明，GO-DEX 和 GO 的通透性分别比 70kDa 葡聚糖高 4.3 倍和 4.9 倍，比 10kDa 葡聚糖高 2.7 倍和 3.1 倍，从而证明了基于 GO 的纳米载体通过有窗孔的内皮屏障具有良好的通透性。
