## 3 Results and Discussion
### Nanocarrier Characteristics  
The nanocarrier characteristics are summarised in Table S2. Of the publications analysed, 88% suggest cancer as the therapeutic application of the study with only two papers not suggesting an application. The size and shape of the nanohybrids varied widely throughout the publications due to the host of different nanohybrids involved; however, most publications recorded at least one of either the height/thickness or size of the system (although these measurements were ill-defined). The height or thickness recorded ranged from 0.8-144 nm, with nine studies reporting it only between 0.8-13 nm. The reported size of the nanocarriers ranged from 35-240 nm. Most papers also compared the size of the functionalised graphene nanocarriers against the size of a single layer GO sheet, which was typically recorded as being between 0.8-1.5 nm in height. The shape and morphology were also varied through the publications; the majority stated that the nanohybrid exhibited a rough surface compared to that of smooth pristine graphene due to the presence of functionalisation. The surface charge ranged from +17.9 mV to -39 mV; unfortunately, this parameter was unrecorded in 47% of studies.  
In 88% of the studies, functionalised GO was used as the nanosystem. Functionalisation included the use of polymers, natural products, dendrimers, metals, and metal oxides. PEG was the most common polymer used; in addition, natural biodegradable and biocompatible polymers, such as hyaluronic acid (1), cellulose (1), chitosan (1), and dextran (1) were also used as functionalising agents. PEG was used in seven publications in combination with other modifications. PEG is a hydrophilic polymer that is used for functionalisation  
Figure 3: A systematic search and inclusion flowchart from the search engines PubMed®, Web of ScienceTM, and Ovid Medline®. Studies were all screened by title, abstract, and by full text to assess their eligibility. A total of seventeen studies were included for analysis based on the predefined inclusion and exclusion criteria.  
to improve the biocompatibility, water dispersity, solubility, and targeting ability of the nanosystem; in addition, PEG offers high efficacy, non-toxicity, non-immunogenicity, and flexibility [67]. PEG is preferentially used over other polymers as it increases the stability of the nanosystem by reducing the risk of aggregation, opsonisation, and phagocytosis. The PEG chains form a voluminous hydrated cloud surrounding the NPs that sterically hinders their interaction with blood components and proteins, thereby facilitating an increase in circulation time by avoiding uptake by the reticuloendothelial system (RES) [79; 80; 81; 82].  
FA was used in three publications as an active targeting agent due to its ability to bind with high affinity to FA receptors (FR). FR are overexpressed in several different human carcinomas, particularly in ovary, breast, lung, and brain cancers [79].  
Metals and metal oxide NPs were also used as functionalities agents, as they can make nanocarriers responsive to different stimuli. Iron oxide (Fe\({}_{3}\)O\({}_{4}\)) NPs are superparamagnetic and can transform electromagnetic energy into heat, which can be used as a trigger for drug release; their incorporation into GO and chitosan microspheres facilitated the nanosystem response to NIR and ultrasound stimulus [73]. Similarly, gold NPs deposited on a GO surface were utilised for their strong absorbance in the visible to NIR region due to their surface plasmon resonance effect in a system that utilised NIR as the release stimulus [78]. Furthermore, some of the publications that utilised pH response as the stimulus also incorporated metals or metal oxides into the nanosystem, offering the opportunity to use combined photothermal and chemotherapy.