# Recent Advances in the Synthesis of Graphene-Based Nanomaterials for Controlled Drug Delivery
## 3 Drug Delivery with Graphene-Based Nanomaterials
### Graphene-Nanoparticle Nanohybrids  
Chemically synthesized GO presents many oxygen-containing groups, such as hydroxyl, carboxylic, and epoxide groups, and therefore various inorganic nanoparticles have been anchored onto the surface of GO or rGO to offer additional optical and magnetic properties. When hybridized with gold or silver nanoparticles, graphene-based nanocarriers can serve as active materials for surface enhanced Raman scattering (SERS) experiments for monitoring the process of drug delivery [37; 38; 56; 59; 79]. When hybridized with magnetic nanoparticles, graphene-based nanomaterials can be used as magnetic materials for MR imaging [36; 39; 46; 47; 80]. Metallic nanoparticles could be used for simultaneous drug delivery and bioimaging of cells. For instance, [PERSON] and co-workers fabricated three-dimensional (3D) spherical nanohybrids by wrapping GO onto gold nanoparticles (Au-GO) through a simple one-step synthesis [37]. The as-prepared Au-GO nanohybrid can not only be used for intracellular Raman imaging in HeLa cells, but can also be exploited to deliver DOX into cancer cells for chemotherapy, as shown in Figure 3. [PERSON] and co-workers conjugated Au nanostars onto the surface of rGO through a seed-mediated growth method, and the synthesized Au@rGO nanocomposites showed an improved colloidal stability, and sensitive SERS response toward Raman-active molecules [79]. These nanocomposites can be used as an active SERS material for anticancer DOX loading and pH-dependent release. In another case, [PERSON] et al., developed a hybrid rGO-loaded ultra-small plasmonic Au nanorod vesicle (~65 nm). The hybrid vesicle exhibited high loading capacity for DOX (65%), and also showed excellent photothermal effect and photoacoustic performance when irradiated with a near infrared laser [59]. Similarly, GO-loaded Ag nanoparticles can also monitor the intracellular release behavior [38; 56]. For instance, [PERSON] et al., synthesized a GO@Ag nanocomposite by the chemical deposition of Ag nanoparticles onto the GO surface via a hydrothermal reaction [38]. The fabricated GO@Ag-DOX nanohybrids could serve not only as a near infrared controlled drug releasing delivery system, but also as both X-ray imaging and tumor photothermal ablation agents. Magnetic metallic oxide nanoparticles could be linked with graphene for stimulation-responsive drug delivery. For instance, [PERSON] et al., modified magnetic Fe3O4 nanoparticles onto the surface of GO  
Figure 3: Schematic illustration of surface enhanced Raman scattering (SERS) based imaging and anticancer drug delivery by using Au@CO. Reproduced with permission from [79]. Copyright Royal Society of Chemistry, 2014.  
nanosheets via an inverse co-precipitation method [80]. The as-prepared Fe\({}_{3}\)O\({}_{4}\)/GO nanocomposites exhibited superparamagnetic property with the saturation magnetization of 63.3 emu g\({}^{-1}\) and significant negative contrast enhancement effect in vitro. The nanocarrier also showed a high loading capacity for 5-fluorouracilacil (0.37 mg mg\({}^{-1}\)), and the drug release can be controlled by the environment's pH. In order to achieve the control of the size and loading amount of the magnetic nanoparticles, they further developed CoFe\({}_{2}\)O\({}_{4}\)/GO nanocomposites by means of a facile sonochemical method [46]. The obtained CoFe\({}_{2}\)O\({}_{4}\)/GO nanohybrids showed superparamagnetic behavior (38.7 emu g\({}^{-1}\)), high hydrophilicity, and ultralow cytotoxicity. Most importantly, the DOX loading capacity of the formed nanocomposites reached 1.08 mg mg\({}^{-1}\). With a complex nanohybrid system, the delivery of drugs can also be controlled. [PERSON] et al., synthesized graphene nanosheet-carbon nanotube-iron oxide nanoparticle nanocomposites (GN-CNT-Fe\({}_{3}\)O\({}_{4}\)) by a green and facile approach.