International Journal of Nanomedicine (Oct 2018)
Controlled quercetin release from high-capacity-loading hyperbranched polyglycerol-functionalized graphene oxide
Abstract
Matin Islami,1 Ali Zarrabi,1 Seiichi Tada,2 Masuki Kawamoto,2,3 Takashi Isoshima,3 Yoshihiro Ito2,3 1Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 8174673441, Iran; 2Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, Wako, Saitama 351-0198, Japan; 3Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan Purpose: 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.Methods: 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.Results: 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 d-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.Conclusion: 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. Keywords: polyglycerol, graphene oxide, hyperbranched polymer, cancer cell
