2.2.2. Graphene Oxide

Another carbon-based nanomaterial for use in biomedical applications is graphene oxide. Nano-graphene oxide complexes, especially metal nanocomposites (nanogold and nanosilver), have been found to be a good choice of material to treat cancer. Due to their greater drug entrapment capability and photothermal and synergizing effects, it is worth highlighting them for their targeted treatment of cancer based on their chemo-thermal behavior.

Chauhan et al. [29] selected gold NPs (AuNPs) as the composite metal and folic acid (FA) as the graphene oxide surface functionalization moiety for active tumor targeting of the model anticancer drug DOX (see Figure 4). Yang et al. [30] have examined the uptake of graphene oxide which has been functionalized with PEG, noting that it has good solubility and biocompatibility. In addition to this, PEG-ylated graphene oxide, which accumulates in tumors and has low retention in the reticuloendothelial system, has also been reported [30].

**Figure 4.** Tumor-localized DOX delivery with simultaneous photothermal ablation [29]. Reproduced with copyright permission from Elsevier, 2017. Legend: FA, folic acid; GO, graphic oxide; AuNPs, gold NPs.

Moreover, Huang et al. [31] have reported that the magnetic functionalized graphene oxide composite may be used as a nanocarrier for the delivery of anticancer drugs. Magnetic graphene oxide was produced by the authors by chemical co-precipitation of Fe3O4 magnetic NPs on graphene oxide nano-platelets. Furthermore, magnetic graphene oxide was modified by chitosan and mPEG-NHS through covalent bonds to synthesize mGOC-PEG. Irinotecan (CPT-11) or DOX was loaded to mGOC-PEG. Another experiment has been reported by Barahuie et al. [32] in which graphene oxide was synthesized in order to explore its potential use as a nanocarrier for an active anticancer agent, chlorogenic acid (CA).

DOX-loaded PEG-ylated nanographene oxide (NGO) preparation has been reported by Zhang et al. [33] where this combination caused destruction of a tumor without recurrence. Qin et al. [34] have used FA-conjugated NGO-PVP as a carrier for DOX, where folate receptors of cancer cells possessed grea<sup>t</sup> affinity to bind with folic acid. The FA-NGO-PVP was delivered within the cytoplasm of folate receptor positive human cervical cancer cells (HeLa). The minimal cellular uptake for the nanocarrier was an indication of the adhering of the FA-NGO-PVP composites to the folate receptors on the surface of the A549 cells. Thus, the nanocarrier was shown to have photo-thermal sensitivity and could be used as an anticancer carrier for chemo-photothermal therapy. Furthermore, camptothecin (CPT) and DOX were involved in the sulfonated NGO sheets, where folic acid was attached to carboxyl groups of the sulfonate NGO sheets to deliver DOX. The cytotoxicity of FA-NGO/CPT/DOX to MCF7 human breast cancer cells has been highlighted elsewhere [35]. Zhao et al. [36] have also prepared pH-responsive chitosan/ graphene oxide nanohybrids to be used for the delivery of DOX anticancer.

Liu et al. [37] have functionalized NGOs with PEG, using these to deliver the SN38 anticancer drug for colon cancer. Masoudipoura et al. [38] have reported a nanographene oxide conjugated with dopamine (DA-nGO) and laden with the anticancer drug methotrexate (MTX) to be supplied to positive human breast adenocarcinoma though adhering to DA receptors. GOs have demonstrated better characteristics when compared to CNTs, owing to their greater drug encapsulation ability. However, their use in biomedical applications is still limited because of their complicated synthesis and lower production yield, which makes them uneconomical.
