nanomaterials Review The Puzzling Potential of Carbon Nanomaterials: General Properties, Application, and Toxicity Danica Jovi´c 1 , Vesna Ja´cevi´c 2,3,4 , Kamil Kuˇca 4,5,* , Ivana Borišev 1, Jasminka Mrdjanovic 6 , Danijela Petrovic 7, Mariana Seke 8 and Aleksandar Djordjevic 1 1 Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovi´ca3, 21000 Novi Sad, Serbia; [email protected] (D.J.); [email protected] (I.B.); [email protected] (A.D.) 2 Department for Experimental Toxicology and Pharmacology, National Poison Control Centre, Military Medical Academy, Crnotravska 17, 11040 Belgrade, Serbia; [email protected] 3 Department of Pharmacological Science, Medical Faculty of the Military Medical Academy, University of Defence, Crnotravska 17, 11000 Belgrade, Serbia 4 Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003 Hradec Kralove, Czech Republic 5 Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 50005 Hradec Kralove, Czech Republic 6 Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia; [email protected] 7 Department of Natural Sciences and Management in Education, Faculty of Education Sombor, University of Novi Sad, Podgoriˇcka4, 25101 Sombor, Serbia; [email protected] 8 Institute of Nuclear Sciences “Vinca”, University of Belgrade, Mike Petrovi´caAlasa 12-14, 11351 Vinˇca, Belgrade, Serbia; [email protected] * Correspondence: [email protected]; Tel.: +420-603-289-166 Received: 6 July 2020; Accepted: 29 July 2020; Published: 31 July 2020 Abstract: Being a member of the nanofamily, carbon nanomaterials exhibit specific properties that mostly arise from their small size. They have proved to be very promising for application in the technical and biomedical field. A wide spectrum of use implies the inevitable presence of carbon nanomaterials in the environment, thus potentially endangering their whole nature. Although scientists worldwide have conducted research investigating the impact of these materials, it is evident that there are still significant gaps concerning the knowledge of their mechanisms, as well as the prolonged and chronic exposure and effects. This manuscript summarizes the most prominent representatives of carbon nanomaterial groups, giving a brief review of their general physico-chemical properties, the most common use, and toxicity profiles. Toxicity was presented through genotoxicity and the activation of the cell signaling pathways, both including in vitro and in vivo models, mechanisms, and the consequential outcomes. Moreover, the acute toxicity of fullerenol, as one of the most commonly investigated members, was briefly presented in the final part of this review. Thinking small can greatly help us improve our lives, but also obliges us to deeply and comprehensively investigate all the possible consequences that could arise from our pure-hearted scientific ambitions and work. Keywords: carbon nanomaterials; fullerene; nanodiamonds; carbon dots; graphene; carbon nanotubes; toxicity; in vitro and in vivo research 1. Introduction Carbon has been extensively investigated, especially in the form of carbon nanomaterials (CNMs), and it seemed to behave like a magnet for the Nobel Prize (in 1996 ”for the discovery of carbon Nanomaterials 2020, 10, 1508; doi:10.3390/nano10081508 www.mdpi.com/journal/nanomaterials Nanomaterials 2020, 10, 1508 2 of 29 Nanomaterials 2020, 10, 1508 2 of 30 1. Introduction atoms bound in the form of a ball,”, and in 2010 ”for groundbreaking experiments regarding the two-dimensionalCarbon has material been graphene”).extensively investigated, In the last four especially decades, in carbon the form has of expanded carbon nanomaterials its family of novel nanomaterials,(CNMs), and which it seem nowed to includes behave like fullerenes, a magnet carbon for the dots Nobel (CD), Prize nanodiamonds (in 1996 ”for the (NDs), discovery nanohorns of carbon atoms bound in the form of a ball,”, and in 2010 ”for groundbreaking experiments regarding (CNHs), nanofibers (CNFs), nanotubes (CNTs), graphene, etc. Carbon nanomaterials usually do the two-dimensional material graphene”). In the last four decades, carbon has expanded its family of not consist of chemical individuals, but form complex mixtures of compounds that only slightly novel nanomaterials, which now includes fullerenes, carbon dots (CD), nanodiamonds (NDs), differnanohorns in molecular (CNH weight,s), nanofibers structure, (CNF isomerism,s), nanotubes etc. (CNT It iss), also graphene, known etc that. Carbon some nanomaterials of these materials possessusually different do not properties consist of andchemical structures individuals, if they but come form from complex different mixtures manufacturers of compounds or arethat evenonly from differentslightly lots. differ Hence, in molecular it is difficult weight, to assess structure, the properties isomerism, of etc. entire It is groupsalso known of materials; that some instead, of these group representativesmaterials possess are discussed. different properties and structures if they come from different manufacturers or Carbonare even from nanomaterials, different lots. as Hence, well it as is their difficult impact, to assess are the greatly properties defined of entire by theirgroups physico-chemical of materials; propertiesinstead, [ 1group–3]. representatives Shape, size, solubility,are discussed. charge, surface, and chemical functionalization of the nanoparticlesCarbon are nanomaterials some of the, as properties well as their that impact, make are the greatly system defined more by or their less physico stable- andchemical prone to properties [1–3]. Shape, size, solubility, charge, surface, and chemical functionalization of the aggregation and self-assembly. By chemical transformation, CNMs can be successfully transformed nanoparticles are some of the properties that make the system more or less stable and prone to into more polar or soluble derivatives, thus overcoming one of the greatest obstacles when it comes aggregation and self-assembly. By chemical transformation, CNMs can be successfully transformed to theinto application more polar in or biological soluble derivatives, media. Anthus inevitable overcoming consequence one of the greatest of the obstacles extensive when production it comes and widespreadto the application application in biological of nanomaterials media. An is inevitable their consequential consequence presence of the extensive in the environment. production and Before theywidespread are settled inapplication soil or continue of nanomaterials to flow within is their water consequential sources, presence nanomaterials in the environment can be transformed. Before as a resultthey of di arefferent settled processes, in soil or continue thus changing to flow theirwithin native water properties sources, nanomaterials [4,5]. Accumulation can be transformed of nanomaterials as in thea soilresult and of water different makes processes these areas, thus nanointoxicated changing their and,native as such,properties with the[4,5] yet. Accumulation unravelled potential of of causingnanomaterials various in e theffects soil in and plants, water animals,makes these fungi, areas microorganisms, nanointoxicated and and,, as consequently, such, with the humans.yet As nanotechnologyunravelled potential has of bloomed causing andvarious still effects has a in lot plants, to go animals, until reaching fungi, microorganisms, its zenith, the impactand, of consequently, humans. As nanotechnology has bloomed and still has a lot to go until reaching its nanomaterials is of utmost importance to be fully addressed. The possible risks [6,7] and toxicity of zenith, the impact of nanomaterials is of utmost importance to be fully addressed. The possible risks nanomaterials (Figure1) have attracted the interest of scientists worldwide. Although a great amount [6,7] and toxicity of nanomaterials (Figure 1) have attracted the interest of scientists worldwide. of researchAlthough has a beengreat performedamount of research so far, thishas been venture performed is still so in far its, infancy.this venture is still in its infancy. In thisIn this review review paper, paper, we we have have selected selected thethe most prominent prominent members members of the of thecarbon carbon nanomaterial nanomaterial family,family briefly, briefly summarized summarized their their main main characteristics characteristics and and potential potential application, application, as well as well as described as described theirtheir toxicity toxicity following following the thein in vitro vitroand andin in vivo vivo results.results. FigureFigure 1. Pros 1. Pros and and cons cons for for the the carboncarbon nanomaterials (CNM (CNMs)s) use use,, original original figure figure.. 2. General Properties of Carbon Nanomaterials Hybridization and bonding between C atoms in carbon nanomaterials are some of the direct guides that classify materials within this group by their properties. For example, all the sp2-structured Nanomaterials 2020, 10, 1508 3 of 30 2. General Properties of Carbon Nanomaterials Nanomaterials 2020, 10, 1508 3 of 29 Hybridization and bonding between C atoms in carbon nanomaterials are some of the direct guides that classify materials within this group by their properties. For example, all the sp2-structured nanomaterialsnanomaterials