## 1 Introduction
Both DOX and camptothecin were loaded with high efficiency through \(\pi\)-\(\pi\) stacking and hydrophobic interactions, and exhibited high cytotoxicity to breast cancer cell line MCF-7 due to the FA receptors on their surface [22; 40]. Alternatively, antibodies, peptides, and aptamers can be utilised as targeting agents for specific cancer cells. [PERSON] et al. have recently developed a GO nanocarrier loaded with DOX that was functionalised with PEG and the HN-1 peptide. The HN-1 peptide has been identified as a small peptide specific to oral squamous cell carcinoma that is able to penetrate tumour tissues. Thus, its incorporation resulted in the increased targeting of cancer cells compared to DOX@NGO-PEG, higher cellular uptake, and cytotoxicity towards oral squamous cell carcinoma cell lines SCC-25 and CAL-27 [39]. As suggested in Table 1, the most extensively researched chemotherapeutic for loading onto GO has been DOX. As DOX is a widely used chemotherapeutic and is efficacious in multiple tumour types, it is useful for in vitro studies. DOX (Figure 2) is an anthracycline antibiotic isolated from the bacterium _Streptomyces peucetius_ var. _casesius_ with molecular formula C\({}_{27}\)H\({}_{29}\)NO\({}_{11}\). After clinical approval in 1963, it has been widely used as a chemotherapeutic in the treatment of solid tumours, including breast, ovarian, lung, and thyroid cancers, and haematological cancers, including leukaemia, as well as both [PERSON]'s and non-Hodgkin's lymphoma [41; 42]. The anthracycline structure, which includes aromatic rings and amino groups, enables DOX to be loaded with high efficiency to graphene and its derivatives through both \(\pi\)-\(\pi\) stacking and electrostatic interactions [23]. DOX can be released from graphene nanocarriers via several different mechanisms, making it an ideal chemotherapeutic for extensive research. The development of graphene nanohybrids as drug delivery vehicles that can respond to release stimuli improves the targeting and specificity of drug delivery further. Smart nanocarriers can release loaded drugs via both internal or external stimuli, including but not limited to pH, temperature, chemical reactions, light, ultrasound, ROS, and magnetic fields [19]. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Graphene-Based** & **Functionalisation** & **Loaded** & **Efficacy Test** & **Stimuli Response** & **Reference** \\
**Nanomaterial** & **Functionalisation** & **Therapeutic** & **Efficacy Test** & **Stimuli Response** & **Reference** \\ \hline GO & Polyethylene-glycol (PEG) & DOX & A549 & Glutathione (GSH) & [26] \\ NGO & PEG & DOX & HeLa & GSH & [27] \\ GO & Poly(vinyl alcohol) (PVA) & Camptothecin & MDA-MD-231 & - & [28] \\ GO & PLA-PEG & Paclitaxel & A549 & - & [29] \\ rGO & Gold nanoclusters & DOX & HepG2 & - & [30] \\ GO & DNA & DOX & HeLa & ATP & [31] \\ GO & FA-PEG & Camptothecin & HeLa & pH & [32] \\ rGO & PEG-BPEI & DOX & PC-3, HeLa & GSH/NIR & [33] \\ GO & PEG & DOX & EMT6 & pH & [34] \\ GOQD & FA-CH & DOX & A549,SH-SV5Y, & & \\ GO & Integrin \(\alpha_{\text{V}}\beta_{3}\) & & MDA-MB 231 & pH & [35] \\ GO & mono-antibody-PEI & DOX & U87 MG, MCF-7 & pH & [36] \\ GO & CMC-HA-FI & DOX & HeLa & pH & [37] \\ GO & Fe\({}_{3}\)O\({}_{4}\), FA & DOX & SK3 & pH & [38] \\ GO & PEG, HN-1 & DOX & OSCC (CAL-27, & & \\  & & & SCC-25) & pH & [39] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Graphene-based nanocarriers developed for drug delivery applications. Further examples have been discussed elsewhere [23; 24; 25]. The release of DOX by a pH-dependent response is one of the most common methods of release. Multi-functionalised GO with hyaluronic acid and the targeting Arg-Gly-Asp peptide, for example, utilised pH response and demonstrated that the cumulative release of DOX after 72 h at a pH of 5.5 was 30.2%, compared to 7.6% at a pH of 7.4 [44]. Delivery systems that pH-responsive are important in cancer treatment as acidic conditions (pH 5-6.5) are characteristic of tumour environments [20; 45; 46; 47].