*DOI: http://dx.doi.org/10.5772/intechopen.103688 Advances in Graphene Platforms for Drug Delivery in Cancer and Its Biocompatibility*

transportation problems through the blood, the binding to the plasma protein corona, and the deposition of QDs in biological fluids and tissues [124]. Due to their size, they can go undetected by the immune system and, if they are not biocompatible, could induce toxicity. The dispersion of these QDs has been achieved with the use of some polymers. However, this can sometimes make the QDs larger and thus recognizable by the immune system [125]. Covalent functionalization of GQDs platforms is easy and simple, given their properties and the high surface area for their functionalization. On the other hand, the binding of non-covalent GQDs is more complicated and unstable and can lead to loss of important functional groups that can, in turn, lead to loss of electronic properties. It is also possible to obtain a wide area of functionalization [126] but the presence of a large, functionalized surface area can have adverse consequences, especially if it is a biologically active ligand that can impact cellular physiological processes. There are currently no studies on real-time monitoring and distribution of GQDs in animal models, so the effect of these platforms remains unknown.

If we want to direct GQD platforms toward specific tumor targets, we must know the molecular biology of the tumor. That is, where they need to be directed and with what do we intend them to interact. To achieve this, we require platforms that can specifically locate and access the tumor and not reach healthy tissue. Unfortunately, as we saw in the previous section, very few of the studies on animal models provide any information on this, since the studies only focus on the effects of GQD platforms at the tumor site but do not mention whether neighboring or distant tissues were affected, if systemic toxic effects were observed, or if there was mortality. The great disadvantage of most nanomaterial platforms, including GQDs, animal models have not yielded enough information about them. All nanomaterials are widely known to be cytotoxic, and so not a single one has been identified as harmless. Therefore, it is important that we obtain detailed information regarding the effects they produce *in vivo*. Additionally, we must remember that inter-individual biological variability is considerable, and it is not always possible to extrapolate data obtained directly from experimental animals to human beings.

Furthermore, all drugs used in clinical oncology are in themselves toxic and produce a variety of adverse effects. While GQD platforms have been used to target specific cells and molecules, most of the studies have been carried out using cells cultured *in vitro*, where the conditions and cellular response are more controlled. Also, only tumor cell lines have been used. There are currently no studies using cell lines from healthy tissue to determine the effect GQDs platforms may have on healthy tissue, either that adjacent to the tumor or healthy cells at a distance. The response of the tumor cell can vary greatly, as well as sensitivity to the GQDs platform and to the delivered drug. One of the big problems when extrapolating these findings to animal models is the dosage and exposure time, since we need to consider the different compartments where the platform will be distributed and the nanomaterial that will be lost during the ADME processes. Another important problem is the scaling of the product: it is not the same to produce the amounts to be used in *in vitro* models, than those needed to treat a laboratory animal, which is generally more complex and expensive. One of the characteristics of GQDs platforms is their large surface area for drug loading. However, more than an advantage, this can have adverse consequences given the large amounts of a certain drug that will be delivered to the cells. One of the great problems of nanobiotechnology is that it has not been possible to determine the exact amount of drug that can be attached to the QDs, nor how much of this actually reaches the target site. We could say that GQDs platforms have a great advantage

insofar as they could have high therapeutic efficacy, but what about safety and specificity? Are they so efficient that they will only target tumor tissue? During the ADME processes, will they not affect other healthy tissues? At most, only five drugs have been used in the production of antitumor drug delivery platforms. Why? Can they not be viably employed with any type of antitumor drug? There are still questions that need to be clarified. If this information is not available, the lack of answers will remain one of the main limitations to these platforms vis-à-vis other nanomaterials.
