# Recent Advances in the Synthesis of Graphene-Based Nanomaterials for Controlled Drug Delivery
## 1 Introduction  
The design and fabrication of gene and drug delivery systems with high loading and release performances are important for improving the therapeutic efficiency of diseases [1; 2]. Previously, various nanomaterials, such as nanoparticles [3], polymers [4; 5], carbon nanotubes [6], and others [7] have been widely used for the controlled drug delivery and release. With the discovery of graphene in 2004 [8], more efforts have been spent to achieve many biomedical applications with graphene-based nanomaterials [9; 10; 11; 12; 13].  
In 2008, [PERSON] and co-worker for the first time reported the synthesis of nanoscale graphene oxide (GO) for drug delivery application [14]. They found that the polyethylene glycol (PEG)-modified GO could be utilized to load the anti-cancer drug doxorubicin by \(\pi\) stacking and kill cancer cells in vitro. After that, graphene has been thought of as an excellent nanocarrier for drug delivery due to several reasons [15; 16]. Firstly, it has a two-dimensional monolayer structure, which could provide a larger surface area for loading more drug than previous nanocarriers. It has been reported that the loading mass of drugs could reach 200% of the graphene-based drug nanocarrier [17]. Secondly, graphene has a high chemical and mechanical stability [18], making graphene-based nanomaterials suitable for different delivery environments. Thirdly, though pristine graphene and graphene oxide (GO) have acertain toxicity to cells and animals, its stability and biocompatibility can be greatly improved by a simple functionalization process, such as coated with biocompatible substance (polyethylene glycol, dextran, alginate, or biomacromolecules), which could reduce or eliminate the cellular toxicity and negative effects to the human body [19; 20]. Finally, graphene and its derivatives are easy to modify with covalent and noncovalent methods [21; 22; 23], and therefore provide more possibilities to synthesize other functional nanohybrids for drug delivery.  
Although graphene and graphene derivatives could be utilized for drug delivery, the loading and release of drug are still difficult to control, such as it generally aggregates in salt or biological solutions and shows a certain degree of cytotoxicity [14; 24; 25]. Therefore, other traditional drug delivery-related nanomaterials, like small molecules, nanoparticles, polymers, and biomacromolecules have been conjugated to graphene to produce novel graphene-based nanohybrids for drug delivery [17; 26; 27; 28]. Previously, several reviews on the synthesis and modification of graphene-based nanomaterials for drug delivery have been reported [29; 30; 31; 32]. For example, [PERSON] et al., summarized the studies (until 2013) on the synthesis of graphene-based nanomaterials for drug delivery and tissue engineering [30], and [PERSON] et al., demonstrated the current advances in the surface engineering of graphene-based nanomaterials for drug delivery [31]. Although great achievements on the drug delivery application of graphene have been obtained, there is still some space left to make it more clear, especially given the recent developments on the design of novel materials for specific drug delivery.  
In this review, we summarized the recent advances (2013-2017) in the synthesis and drug delivery application of graphene-based nanomaterials. We focused on the modification of graphene with other materials, such as small molecules, nanoparticles, polymers, and biomolecules. This review will be helpful for understanding the drug delivery mechanisms of materials, the functionalization of graphene, and the design of functional hybrid nanomaterials for various applications.