# Recent Advances in the Synthesis of Graphene-Based Nanomaterials for Controlled Drug Delivery
## 2 Ways of Controlled Drug Delivery
### Exogenous Stimuli-Responsive Drug Delivery  
Temperature-stimulated drug deliveryTwo temperature-responsive controlled delivery systems currently exist. One is composed of temperature-sensitive nanogels (or composite particles), the volumes of which vary because of the changes in temperature. The drug delivery in this system is based on the changes of the volume of nanogels [62]. The other is composed of amphiphilic polymer \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Stimulus** & **Nanocarrier** & **Stabilizer** & **Drug** & **Targets** & **Reference** \\ \hline \multirow{6}{*}{pH} & rGO & FA & Dox & MDA-MB 231 cells & [43] \\  & GNS & starch & HCPT & SW-620 cells & [44] \\  & GQDs & RGD & Dox & DU-145, PC-3 cells & [45] \\  & CoFe\({}_{2}\)O\({}_{4}\)/GO & - & Dox & HeLa cells & [46] \\  & GNS/CNT/Fe\({}_{3}\)O\({}_{4}\) & - & 5-FU & HepG2 cells & [47] \\  & GODs@MSN & - & Dox & A549 cells & [48] \\  & GO & HA & Epirubicin & B16F1 cells & [49] \\  & GO & HA & Dox & H22 hepatic cells & [50] \\  & GO & RC & Dox & Hepatamons cells & [51] \\  & GO & CMC, LA & Dox & SMMC-7721 cells & [52] \\  & GdGODs & FA & Dox & HeLa, HepG2 cells & [53] \\ \hline \multirow{2}{*}{Enzyme} & GO & PEG, peptide & Dox & A549 cells & [54] \\  & GONR & DSPE-PEG & Lucanthone & U25 cells & [55] \\ \hline \multirow{2}{*}{Redox} & GO/Ag & PEI & Dox & HeLa cells & [56] \\  & GO & ALG-PEG & Dox & HepG2 cells & [57] \\ \hline \multirow{3}{*}{Multi} & GO & HA & Dox & MDA-MB 231 cells & [58] \\  & rGO/Au & - & Dox & U87 MG cells & [59] \\  & GO/MSN & - & Dox & MCF-7 cells & [60] \\  & rGO & BPEI, PEG & Dox & PC-3 cells & [61] \\ \hline \hline \end{tabular}  
* 1 PTX: paditaxel; GO: graphene oxide; PNP: polymer nanoparticles; ADR: Adriamu; NGR: Asn-Gly-Arg peptide; PPS: poly(pyrrole); DEX: dexamethasone; FA: folic acid; GNS: Graphene nanosheets; HCPT: Hydroxyemptotheci; GQDs: graphene quantum dots; RGD: arginine-glycine-asparatic acid; 5-FU: 5-fluorouracil; MSN: mesoporous silica nanoparticles; HA: hyaluronic acid; RC: Cyclic RGD/chitosan; CMC: carboxymethyl chitosan; LA: lactobionic acid; PEG-DSPE: 1-2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol); GONR: graphene oxide nanoribbons; PEI: polyethylenimine; ALG-PEG: PEGylated alginate.  
\end{table} 
Table 1: _Cont._  
Figure 1: Ways of controlled drug delivery for various biomedical applications. AMF: alternating magnetic fields; NIR: near-infrared irradiation; DTT: dithiothreitol. micelles. In this system, the changes of temperature affect the solubility of temperature-sensitive block copolymers in solutions and cause the destruction of micellar structures [63]. These processes facilitate the drug delivery. For instance, [PERSON] et al., reported that the drug loading and release of the thermos-sensitive graphene oxide-polymer nanoparticles hybrid could be controlled by adjusting temperature [35]. _Magnetic field-stimulated drug delivery._ Magnetic fields enable magnetic localization and local heating in vitro and in vivo. A constant external magnetic field can promote the aggregation of magnetic nanoparticles, which carry drugs at the location of the tumor. These magnetic nanoparticles exhibit hysteresis loss and/or Neel relaxation, and thus can serve as transducers to raise the temperature at a specific location within alternating magnetic fields (AMF), thus greatly speeding up the rate of drug release [64]. For example, the polymer stabilized Fe\({}_{3}\)O\({}_{4}\)-Graphene could rapidly release its loaded drug under an alternating magnetic field. _Uultrasound-stimulated drug delivery._ Drugs can be delivered in large quantities from components that are subjected to continuous heating by ultrasound stimulation. Pulse ultrasound can be used for mechanical crushing, which undermine the stability of drug nanocarrier systems and significantly increases the amount of drug released within a short period [65].