Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 8174673441, Iran,
Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, Wako, Saitama 351-0198, Japan.
Int J Nanomedicine. 2018 Oct 5;13:6059-6071. doi: 10.2147/IJN.S178374. eCollection 2018.
An efficient drug-delivery system was prepared based on graphene oxide using a facile and one-step strategy for controlling the release of anticancer drugs.
Fabrication of single-layer graphene oxide (GO) sheets was carried out by both modified and improved Hummers method. Biocompatible hyperbranched polyglycerol (HPG) was grafted on the surface of GO through the ring-opening hyperbranched polymerization of glycidol. Various ratios of GO and glycidol were used for polymer grafting. An anticancer drug, quercetin (Qu), was loaded into modified GO via noncovalent interactions.
Polymer grafting on the surface of GO sheets was confirmed by results obtained from Fourier-transform infrared and Raman spectroscopy, thermogravimetric analysis, energy-dispersive X-ray and X-ray spectroscopy, scanning electron microscopy, and atomic force microscopy. It was revealed that polymerization increased -spacing between the basal planes. In addition, as a hydrophilic polymer, HPG improved the stability and dispersion of GO sheets in biological solutions and endowed extra drug-loading capacity for the sheets. The effect of hyperbranched structure on drug loading and release was investigated by comparing drug loading and release for HPG-modified GO and linear PPO-modified GO. Our experiments indicated high drug-loading capacity (up to 185%), and excellent encapsulation efficiency (up to 93%) for HPG-GO compared to linear PO-grafted GO. The release profile of Qu under various pH levels exhibited controlled and sustained drug release without an initial burst effect for HPG-GO, suggesting that an acidic solution could facilitate drug release. HPG-GO did not show any cytotoxicity on the MCF7 cell line in different concentrations during 72 hours' incubation. Uptake and entrance of HPG-GO into the cells were verified by determining the intracellular amount of Qu by high-performance liquid chromatography.
A combination of the unique properties of GO and the biodegradable polymer polyglycerol revealed high drug-loading capacity, pH-dependent drug release, and cytocompatibility with HPG-GO, thus introducing it as a promising nanocarrier for anticancer drug delivery.
本研究通过简便的一步法策略，基于氧化石墨烯（GO）制备了一种高效的药物输送系统，以控制抗癌药物的释放。
采用改良和改进的 Hummers 法制备单层 GO 片。通过环氧丙烷的开环支化聚合将生物相容性的超支化聚甘油（HPG）接枝到 GO 表面。使用不同比例的 GO 和环氧丙烷进行聚合物接枝。通过非共价相互作用将抗癌药物槲皮素（Qu）载入改性 GO 中。
通过傅里叶变换红外和拉曼光谱、热重分析、能量色散 X 射线和 X 射线能谱、扫描电子显微镜和原子力显微镜的结果证实了 GO 片表面的聚合物接枝。结果表明聚合增加了基面之间的层间距。此外，作为一种亲水性聚合物，HPG 提高了 GO 片在生物溶液中的稳定性和分散性，并赋予了 GO 片额外的载药能力。通过比较超支化结构改性 GO 和线性 PPO 改性 GO 的载药和释放，研究了超支化结构对载药和释放的影响。我们的实验表明，与线性 PO 接枝 GO 相比，HPG-GO 具有较高的载药能力（高达 185%）和优异的包封效率（高达 93%）。在不同 pH 值下，Qu 的释放曲线表现出无初始突释效应的控制和持续释放，表明酸性溶液可以促进药物释放。在 72 小时孵育过程中，不同浓度的 HPG-GO 对 MCF7 细胞系均无细胞毒性。通过高效液相色谱法测定细胞内 Qu 的含量，验证了 HPG-GO 进入细胞的摄取和进入。
GO 的独特性质与可生物降解聚合物聚甘油的结合，使 HPG-GO 具有高载药能力、pH 依赖性药物释放和与细胞的相容性，因此将其作为一种有前途的抗癌药物输送纳米载体。
