## 3 Graphene and Graphene-Related Materials for Biological Applications
### Graphene and Related Materials as Drug Delivery Platforms  
The most investigated biological application of graphene and related materials' still remains drug delivery [91]. The ability of materials to drag and drop chemicals in the human body environment is well exploited by graphene and graphene-related materials [81]. [PERSON] et al. [92] described the interactions between graphene and proteins elucidating the ability of graphene-based materials to trigger several protein complexes on the cellular membrane to facilitate uptake. This was due to both electron transfer and residual functionalities on graphene-like materials' surface. [PERSON] et al. [93] deeply explored the relationship between graphene's surface topological defects and its ability of drug delivery, proving a strong effect of topology. The authors described the folding ability of these materials in several shapes ranging from nanoscrolls to polyhedral ones. This protein ability allows different interactions with different folding agents such as membrane proteins or nucleic acids. A further study by [PERSON] et al. [94] theoretically clarified the loading ability of pristine and metal-decorated graphene materials. Among them, hydrogel and foam are the most attracting solutions because drug release could be triggered by both chemical and thermal modifications [95]. [PERSON] et al. [96] produced a biocompatible graphene foam surface tailored with alanine, cysteine, and glycine for cisplatin drug and release. The authors tested the material with a high load of cisplatin on MCF-7 and HepG2 human cancer cell lines with good results. Additionally, the graphene-based carrier underwent biodegradation inside the body according to the mechanism reported in Figure 2.  
Authors clearly described that after cellular death the graphene foam was degraded by both reactive oxygen radicals and hydrolytic enzymes. Furthermore, the degradation pathway lead to the formation of carbon dioxide without highly toxic metabolites. [PERSON] et al. [97] studied the release of cisplatin in a very complex graphene-based system containing chitosan, magnetite, and silicon dioxide. By a combination of empirical studies and density functional theory calculation, authors showed that the presence of graphene improved the releasing potentiality up to 91% compared with the other samples tested. Graphene and related materials also represent a very promising platform for drug release upon biological stimuli, as reported by [PERSON] et al. [98] in the case of doxorubicin. Doxorubicin is a widely diffused anticancer drug acting on the S phase of the cellular metabolic pathway [99]. Several studies reveal the efficacy of graphene-based materials as carriers for doxorubicin as reported by [PERSON] et al. [100]. Contrary to polymer-based formulations, graphene and graphene-like materials could act not merely as delivery systems but also as smart platforms to target and release doxorubicin upon several stimuli on a large time window and to monitor the cell vitality [101]. Furthermore, graphene-like materials could be also coupled with polymers to enhance classical formulation effects. The authors proved the effectiveness of chitosan-tailored graphene materials as carriers through molecular dynamic calculation. Doxorubicin interacts with both the \(\pi\) orbital system of graphene and the polar functionalities of the chitosan. After reaching the target, doxorubicin interacts with protein amine and carboxylic residues losing the chitosan interactions. In this case, the weak interactions with the graphene surface are not sufficient, and it was efficiently released. This effect was magnified considering that the base of the drug delivery systems is the pH release mechanism [102]. [PERSON] et al. [103] described a pH-responsive, GO-based functionalized chitosan nanocomposite for doxorubicin delivery.