Carbon-based nanomaterials including carbon nanotubes, graphene oxide, fullerenes and nanodiamonds are potential candidates for various applications in medicine such as drug delivery and imaging. However, the successful translation of nanomaterials for biomedical applications is predicated on a detailed understanding of the biological interactions of these materials. Indeed, the potential impact of the so-called bio-corona of proteins, lipids, and other biomolecules on the fate of nanomaterials in the body should not be ignored. Enzymatic degradation of carbon-based nanomaterials by immune-competent cells serves as a special case of bio-corona interactions with important implications for the medical use of such nanomaterials. In the present review, we highlight emerging biomedical applications of carbon-based nanomaterials. We also discuss recent studies on nanomaterial 'coronation' and how this impacts on biodistribution and targeting along with studies on the enzymatic degradation of carbon-based nanomaterials, and the role of surface modification of nanomaterials for these biological interactions. Advances in technology have produced many carbon-based nanomaterials. These are increasingly being investigated for the use in diagnostics and therapeutics. Nonetheless, there remains a knowledge gap in terms of the understanding of the biological interactions of these materials. In this paper, the authors provided a comprehensive review on the recent biomedical applications and the interactions of various carbon-based nanomaterials.

Titanium dioxide (TiO₂), also known as titanium (IV) oxide or anatase, is the naturally occurring oxide of titanium. It is also one of the most commercially used form. To date, no parameter has been set for the average ambient air concentration of TiO₂ nanoparticles (NP) by any regulatory agency. Previously conducted studies had established these nanoparticles to be mainly non-cyto- and -genotoxic, although they had been found to generate free radicals both acellularly (specially through photocatalytic activity) and intracellularly. The present study determines the role of TiO₂-NP (anatase, ∅ < 100 nm) using several parameters such as cyto- and genotoxicity, DNA-adduct formation and generation of free radicals following its uptake by human lung cells in vitro. For comparison, iron containing nanoparticles (hematite, Fe₂O₃, ∅ < 100 nm) were used. The results of this study showed that both types of NP were located in the cytosol near the nucleus. No particles were found inside the nucleus, in mitochondria or ribosomes. Human lung fibroblasts (IMR-90) were more sensitive regarding cyto- and genotoxic effects caused by the NP than human bronchial epithelial cells (BEAS-2B). In contrast to hematite NP, TiO₂-NP did not induce DNA-breakage measured by the Comet-assay in both cell types. Generation of reactive oxygen species (ROS) was measured acellularly (without any photocatalytic activity) as well as intracellularly for both types of particles, however, the iron-containing NP needed special reducing conditions before pronounced radical generation. A high level of DNA adduct formation (8-OHdG) was observed in IMR-90 cells exposed to TiO₂-NP, but not in cells exposed to hematite NP. Our study demonstrates different modes of action for TiO₂- and Fe₂O₃-NP. Whereas TiO₂-NP were able to generate elevated amounts of free radicals, which induced indirect genotoxicity mainly by DNA-adduct formation, Fe₂O₃-NP were clastogenic (induction of DNA-breakage) and required reducing conditions for radical formation.

Graphene oxide (GO) undergoes neutrophil myeloperoxidase (MPO) dependent degradation and the degradation products are non-genotoxic for human lung cells.

Cellulose is widely used as a thickener and filler in foods and drugs. It has been designated “generally regarded as safe” (GRAS). Nanocellulose (NC) has many additional potential applications designed to improve food quality and safety, but has not yet been designated as GRAS. Here we present results of toxicological studies of ingested NC in physiologically relevant in vitro and in vivo systems. In vitro studies employed a gastrointestinal tract simulator to digest two widely-used forms of NC, nanocellulose fibrils (CNF) and cellulose nanocrystals (CNC), at 0.75 and 1.5% w/w, in a fasting diet as well as in a standardized food model based on the average American diet. A triculture model of small intestinal epithelium was used to assess effects of a 24 hour incubation with the digested products (digesta) on cell layer integrity, cytotoxicity and oxidative stress. Other than a 10% increase over controls in reactive oxygen species (ROS) production with 1.5% w/w CNC, no significant changes in cytotoxicity, ROS or monolayer integrity were observed. In vivo toxicity was evaluated in rats gavaged twice weekly for five weeks with 1% w/w suspensions of CNF in either water or cream. Blood, serum, lung, liver, kidney, and small intestine were collected for analysis. No significant differences in hematology, serum markers or histology were observed between controls and rats given CNF suspensions. These findings suggest that ingested NC has little acute toxicity, and is likely non-hazardous when ingested in small quantities. Additional chronic feeding studies are required to assess long term effects, and potential detrimental effects on the gut microbiome and absorbance of essential micronutrients. These studies are underway, and their outcome will be reported in the near future.