## 3 Results and Discussion
### Experimental Conditions  
#### 3.3.1 Payload Characteristics and Drug Loading  
Following the predefined inclusion criteria, all of the analysed studies were those that used the small molecule chemotherapeutic drug DOX as the payload (Table S3). The drug loading content (DLC) reflects the amount of loaded drug compared to the mass of the nanocarrier. The drug loading efficiency (DLE), on the other hand, reflects the amount of drug loaded on the nanocarrier against the amount of drug provided to the system; both parameters are recorded in Table S3.  
The DLC ranges from 9.26-346%, and the DLE ranges from 50.0-99.7%. It was expected that of the two, the DLE would be higher, as it is often harder to obtain a high loading content [83]. This is the case for 71% of papers that recorded both parameters. For GO-PAC/HEC, however, the increase in the ratio of DOX to GO causes an increase in DLC from 49% at a ratio of 1:0.5 GO:DOX to 216% at a ratio of 1:4; a decrease in the DLE from 98% at 1:0.5 to 54% at the ratio of 1:4 was also observed [64]. Similar results were recorded for the NGO-HDex nanohybrid, which also exhibited a higher DLC to drug embedding efficiency [71]. Unfortunately, only 41% of the publications reported both the DLC and the DLE, although all publications reported at least one parameter.  
These data offer examples of high DLC and high DLE of DOX onto the graphene-based nanocarriers. This outcome can be attributed to the high surface area of graphene and its derivatives. In addition, the aromatic structure of DOX facilitates the \(\pi\)-\(\pi\) stacking onto graphene. Moreover, the functional groups on both DOX and GO allow strong hydrogen bonding to occur. The range in different loading efficiencies throughout the publications can be attributed to the variety of functionalisation methods that were used. It has been reported that functionalisation can either help or hinder the loading efficiency of a drug onto a nanocarrier. A compromise must be met between keeping a relatively high loading efficiency but also using a functional, non-toxic, and biocompatible nanocarrier.  
The Zn-d 3-rGO nanohybrid offers a high loading efficiency of 99.7%, which may be attributed to the presence of Zn\({}^{2+}\) and the formation of a complex between this positive Zn ion and the -O-H and -O groups on DOX; the complex traps DOX onto the nanocarrier, in addition to hydrogen bonding and \(\pi\)-\(\pi\) stacking of DOX with GO [68]. [PERSON] and [PERSON] suggested that the presence of PEG in their GO-TD-Fe\({}_{3}\)O\({}_{4}\)@PEG prevented the diffusion of DOX into the solution, thereby facilitating high loading efficiency in addition to electrostatic interactions, \(\pi\)-\(\pi\) stacking, hydrogen bonding, and hydrophobic interactions [67].  
On the other hand, the loading efficiencies of the two non-functionalised GO nanosystems were high, at 93.6% and 91% [72,77]. It has been suggested that the presence of functionalisation groups on graphene nanocarriers can hinder the loading efficiency of DOX due to their bulkiness [84]. Further supporting this, [PERSON] et al. showed that the GO-HA-RGD/DOX nanosystem had a DLE of 72.9% compared to GO/DOX and GO-HA/DOX, which had loading efficiencies of 90.1% and 76.3%, respectively [44].