key: cord-0027130-04dyp5c0 authors: Rozhin, Petr; Abdel Monem Gamal, Jada; Giordani, Silvia; Marchesan, Silvia title: Carbon Nanomaterials (CNMs) and Enzymes: From Nanozymes to CNM-Enzyme Conjugates and Biodegradation date: 2022-01-28 journal: Materials (Basel) DOI: 10.3390/ma15031037 sha: 8492989133f5f5b2f3df96f1fc91c9d4037588da doc_id: 27130 cord_uid: 04dyp5c0 Carbon nanomaterials (CNMs) and enzymes differ significantly in terms of their physico-chemical properties—their handling and characterization require very different specialized skills. Therefore, their combination is not trivial. Numerous studies exist at the interface between these two components—especially in the area of sensing—but also involving biofuel cells, biocatalysis, and even biomedical applications including innovative therapeutic approaches and theranostics. Finally, enzymes that are capable of biodegrading CNMs have been identified, and they may play an important role in controlling the environmental fate of these structures after their use. CNMs’ widespread use has created more and more opportunities for their entry into the environment, and thus it becomes increasingly important to understand how to biodegrade them. In this concise review, we will cover the progress made in the last five years on this exciting topic, focusing on the applications, and concluding with future perspectives on research combining carbon nanomaterials and enzymes. Carbon nanomaterials (CNMs) and enzymes belong to two scientific fields that have been traditionally widely separated, and research at their interface bears a number of challenges to overcome, both experimentally and culturally [1] . Nevertheless, in recent years a number of studies have allowed great progress in this research area, pushing the limits of what was considered possible, and demonstrating great innovation potential for a wide number of applications. Enzymes can be covalently conjugated onto nanocarbons, adsorbed on their surface, or even encapsulated in those with a hollow structure, as reviewed elsewhere [2] [3] [4] [5] . The interactions between proteins and nanocarbons can play an important role in determining their fate in vivo, including their biodegradation [6] [7] [8] , formation of a biocorona [9] [10] [11] , and consequent modulation of the immune response [12] . Besides the exciting area of biointegration of nanocarbons, for instance for the regeneration of conductive tissues [13] , and (flexible) bioelectronics' development [14] , the fields of sensing and diagnostics [15] certainly benefit from the inclusion of both nanocarbons and enzymes. Finally, considering the current emergency we are facing in terms of environmental impact of human activities and climate change that requires urgent action, the use of enzymes is very attractive for the production, modification, and degradation of nanocarbons to render the relevant processes more sustainable. To provide a general overview of the diverse members of each family, this minireview will briefly introduce the classification of enzymes and nanocarbons, followed by an 1. The first component refers to the general type of reaction being catalyzed. For instance, EC 1 indicates oxidoreductases that catalyze redox reactions, and EC 3 identifies hydrolases that catalyze hydrolytic reactions ( Figure 1 ). The second number indicates the subclass based on the type of compound or functional group involved in the reaction. For example, EC 1.13 refers to oxygenases that insert oxygen on the substrate, and EC 2.3 indicates acyl-transferases that transfer acyl groups, etc.). The third component denotes the sub-subclass, by further specifying the reaction being catalyzed, for instance in terms of acceptors, or specific groups being transferred. As an example, EC 2.1.1 indicates methyl transferases. The fourth component is simply a serial number that refers to the specific enzyme. To provide a general overview of the diverse members of each family, this minireview will briefly introduce the classification of enzymes and nanocarbons, followed by an overview of the literature describing their combination. We will then discuss the recent progress in a variety of applications, focusing on the last five years, and directing the reader to reviews of each topic where older research can be found. Finally, we will conclude with a perspective towards the future of this exciting research area. Enzymes have attracted scientists' attention for a long time. It is imperative to adopt an unambiguous nomenclature and classification for this enormous and diverse group of biological catalysts to permit their rigorous study and accelerate scientific progress in this area. The International Union of Biochemistry and Molecular Biology (IUBMB) has introduced the IUBMB ExplorEnz website [16] , where it is possible to navigate the Enzyme Commission (EC) system, which uses four-component numbers to identify each enzyme (i.e., EC X.X.X.X): 1. The first component refers to the general type of reaction being catalyzed. For instance, EC 1 indicates oxidoreductases that catalyze redox reactions, and EC 3 identifies hydrolases that catalyze hydrolytic reactions ( Figure 1 ). 2. The second number indicates the subclass based on the type of compound or functional group involved in the reaction. For example, EC 1.13 refers to oxygenases that insert oxygen on the substrate, and EC 2.3 indicates acyl-transferases that transfer acyl groups, etc.). 3. The third component denotes the sub-subclass, by further specifying the reaction being catalyzed, for instance in terms of acceptors, or specific groups being transferred. As an example, EC 2.1.1 indicates methyl transferases. 4 . The fourth component is simply a serial number that refers to the specific enzyme. However, the system presents room for improvement, because it is not always unambiguous. In fact, new classes are constantly being added to the EC system, and it should also be noted that non-physiologically occurring enzymes are not included [17] . For these reasons, many other databases can be useful to complement the ExplorEnz information. For instance, helpful information can be found in the relevant metabolic pathways described on KEGG [18] , kinetic data on BRENDA [19] , thermodynamic data on NIST [20], opened the way to decades of research that have provided several routes for its chemical functionalization, as recently reviewed [79] . Further tailoring of C 60 properties can be attained through doping with heteroatoms [80] . Molecular confinement also offers the possibility to encase other elements in their interior to provide endohedral fullerenes [81] with interesting properties [82] . Fullerenes are fascinating molecules that have attracted researchers' interest as they can be formed in space [83] . On Earth, they have been proposed for various applications, including the targeted delivery of therapeutics [84] and innovative antiviral therapies [85] . Despite the many potential uses in medicine [86] , especially in photodynamic cancer therapy thanks to their ability to generate and modulate reactive oxygen species (ROS) levels [87] , their electronic properties thus far found translation mainly in the field of photovoltaics, thanks to their electron-acceptor nature [88] and electron-transport ability [89] . Multiple fullerenes can be organized one inside another in carbon nano-onions (CNOs) [27] . These concentric, multi-layered fullerenes can have a size ranging from 2 to 100 nm, depending on the method of synthesis [90] . Generally, multi-fullerenes display a decreasing reactivity with increasing size, corresponding to decreasing curvature, and therefore, the associated strain on the CNO surface. Consequently, small CNOs present good reactivity, although it should be noted that also other factors, such as the production method and the consequent amount of defect sites, affect their reactivity [91] . In the last decade, their biological [92, 93] and electrochemical [94, 95] applications have significantly expanded due to the favorable properties of the nanomaterial, including their small size, large accessible surface area, and high biocompatibility [96] [97] [98] , especially once they are rendered soluble through covalent and non-covalent functionalization [99] [100] [101] [102] [103] . It is worth noting that recent findings described white-light luminescence arising when CNOs were produced through pyrolysis and underwent oxidative treatments [104] . Carbon nanocones [105] can form clusters termed carbon nanohorns (CNHs) [106] . Like many other CNMs, pristine nanocones unfortunately tend to aggregate in many solvents, and they do so in various morphologies termed dahlia-, bud-, or seed-like CNHs [107] . Despite this limitation, they can find promising applications in biosensing [108] , medicine [109] , and electrocatalysis [110] , sometimes even outperforming other CNMs [111] , and with relevance to clean energy [112] and carbon dioxide fixation [113] . There are not many studies on CNHs relative to the other CNMs, possibly also due to a more limited number of commercial sources. As a result, this type of nanomaterial remains an underexplored opportunity for innovation in numerous fields. In the last few years, luminescent carbon dots (CNDs) have emerged for their innovation potential, especially in sensing and biomedicine [114, 115] , thanks to their low-toxicity, chemical inertness, ease of preparation, environmental friendliness, and interesting physicochemical properties [116, 117] . Another key advantage relative to many other CNMs, is the excellent solubility of CNDs in a large variety of solvents, both organic and aqueous, depending on their chemical nature [118] . These nanomaterials have attracted great attention for their cost-efficient and sustainable production [119] , using, for instance, natural products [120, 121] or biomass waste as carbon source [122] . However, the fine tailoring of their desired optical properties has been challenging [123] . Indeed, the exact chemical structure of CNDs still poses many unanswered questions [124, 125] , and the thorough use of spectroscopic methods is key to providing an accurate characterization of the emittive species [126] . As we advance our understanding of CNDs' nature, further prospects open up [127] , expanding their applications to organocatalysis [128] , sensitizers for photocatalysis [129] and pollutant [130] , and to energy conversion and storage [131] , as capacitor electrodes, for instance [132] . NDs are characterized by sp 3 -hybridization of their carbon core. NDs come in different sizes, morphologies, and surface types, depending on the method used for their preparation and functionalization [133] . They display attractive physico-chemical properties such as hardness, biocompatibility, and chemical inertness, leading to research on a variety of potential biological uses, especially delivery of therapeutics and imaging [134, 135] , but also sensing [136] , tissue regeneration [137] , skin products' formulations [138] , and in polished or active coatings with antimicrobial, antifriction, and mechanical reinforcing properties [139] . Recently, NDs have been considered also for their use in theranostics as applied to neurodegenerative diseases, thanks to their additional benefit of crossing the blood-brainbarrier [140] . Other emerging areas of application include primarily biological use in cells [141, 142] and in vivo [143] , but also catalysis [144] . Carbon nanotubes can be composed of one graphitic layer rolled up in single-walled CNTs (SWCNTs) [145] , or multiple coaxial graphitic nanotubes called multi-walled CNTs (MWCNTs) [146] , which can be grown with branches also [147] . CNTs can have very different properties; for instance, they can be semiconducting or metallic, depending on their type and chirality [148] . Over the years, several functionalization strategies have been developed [149] ; oxidation is by far the most popular way to increase their polarity and dispersibility in various solvents, including water [150] . Therefore, fine control over their synthesis, purity and, thus, homogeneity is critical to enable their translation into large-scale use [151] and to fill the gap between their properties as individual CNTs and those of their bundled aggregates-often a practical limitation for industrial use [152] . CNTs have attracted great interest although there are still challenges to overcome to enable a wider commercial use of their unique properties [153] . Key areas of application include various types of high-performing composite materials, where demands of conductivity, robustness, flexibility, and mechanical resistance are high [154] . These include artificial neuromuscular prostheses [155, 156] , and more generally nano-bioelectronics [157] and wearable electronics [158] , but also sensing [159] and imaging [160] , orthopedic devices [161] , tissue regeneration and biomedical use [162] [163] [164] , electroactive materials for environmental and energy technology [165] [166] [167] [168] [169] [170] [171] , electronics and computing [172, 173] , and various forms of catalysis [174] [175] [176] [177] [178] [179] . In the last decade, the most popular carbon allotrope has been graphene (G), which can be considered as a 2D layer of sp 2 -hybridized carbon atoms arranged in a honeycomb lattice. It is worth noting that G can come in many forms, in terms of size, layers, level of oxidation, etc. which will all affect its physico-chemical properties [180] . In particular, graphene oxide (GO) [181, 182] or its reduced form (rGO) [183, 184] are often used for their improved dispersibility, relative to pristine G. G properties have also been tailored through topology [185] , such as twists and nanoribbons [186] . Given the large heterogeneity in size, number of layers and of defects of G flakes, the general term of graphene-based materials is preferred over just G, to refer to this sub-class of CNMs [187] . Applications are similar to CNTs, and they include composite reinforcement [188] , wearable [189] and flexible electronics [190, 191] , including memory devices [192] and even stretchable batteries [193] , energy storage [194] and conversion [195] [196] [197] [198] , environmental remediation [199, 200] , varying types of catalysis [201] [202] [203] [204] , and innovative uses in the healthcare sector [205] , such as regenerative medicine [206] and sensing [207, 208] . In this case, large-scale, cost-effective production of high-quality G [209, 210] and standardization are key for the translation of G properties into commodity products at a global level [211] . A literature search for the term "enzyme" in conjunction with each one of the most popular CNMs shown in Figure 2 , in the title, abstract, or keywords, has revealed that the vast majority of scientific articles pertain to CNTs (4.3 × 10 3 documents), followed by G (3.4 × 10 3 documents). However, in the last decade (Figure 3 ), scientific works on either one averaged about 300 per year, with a slight decrease for CNTs after 2017, opposed to a continuous increase for G up to 2019, surpassing CNTs in 2015. This trend could be related to concerns over CNTs' toxicity, as suggested by the fact that scientific documents on this topic peaked at nearly 300 in 2015, and since then held steady. However, given their high innovation potential in medicine [212, 213] , and the high number of variables that affect their biocompatibility [214, 215] , alarming generalizations to ban their use are best avoided [216] . neity in size, number of layers and of defects of G flakes, the general term of graphenebased materials is preferred over just G, to refer to this sub-class of CNMs [187] . Applications are similar to CNTs, and they include composite reinforcement [188] , wearable [189] and flexible electronics [190, 191] , including memory devices [192] and even stretchable batteries [193] , energy storage [194] and conversion [195] [196] [197] [198] , environmental remediation [199, 200] , varying types of catalysis [201] [202] [203] [204] , and innovative uses in the healthcare sector [205] , such as regenerative medicine [206] and sensing [207, 208] . In this case, large-scale, cost-effective production of high-quality G [209, 210] and standardization are key for the translation of G properties into commodity products at a global level [211] . A literature search for the term "enzyme" in conjunction with each one of the most popular CNMs shown in Figure 2 , in the title, abstract, or keywords, has revealed that the vast majority of scientific articles pertain to CNTs (4.3 × 10 3 documents), followed by G (3.4 × 10 3 documents). However, in the last decade (Figure 3 ), scientific works on either one averaged about 300 per year, with a slight decrease for CNTs after 2017, opposed to a continuous increase for G up to 2019, surpassing CNTs in 2015. This trend could be related to concerns over CNTs' toxicity, as suggested by the fact that scientific documents on this topic peaked at nearly 300 in 2015, and since then held steady. However, given their high innovation potential in medicine [212, 213] , and the high number of variables that affect their biocompatibility [214, 215] , alarming generalizations to ban their use are best avoided [216] . In comparison to CNTs and G, all the other CNMs lagged behind, each one reaching far less than 100 in total-with two exceptions-and representing today a missed opportunity for research. The first exception was fullerenes, possibly since they were the first to be discovered and thus have had more years of related research, reaching just over 600 records. The second exception was CNDs, which are among the most recent CNMs to be discovered. Scientific papers on CNDs have been increasing steadily year after year, since the first ones appeared in 2004. Therefore, it is foreseeable that CNDs will keep rising in popularity in the immediate future, although there is still a long way ahead to approach the numbers seen for CNTs and G. In terms of applications, most studies pertain biosensing and biofuel cells (Table 1) , although biocatalysis and biomedical applications other than sensing have been pursued In comparison to CNTs and G, all the other CNMs lagged behind, each one reaching far less than 100 in total-with two exceptions-and representing today a missed opportunity for research. The first exception was fullerenes, possibly since they were the first to be discovered and thus have had more years of related research, reaching just over 600 records. The second exception was CNDs, which are among the most recent CNMs to be discovered. Scientific papers on CNDs have been increasing steadily year after year, since the first ones appeared in 2004. Therefore, it is foreseeable that CNDs will keep rising in popularity in the immediate future, although there is still a long way ahead to approach the numbers seen for CNTs and G. In terms of applications, most studies pertain biosensing and biofuel cells (Table 1) , although biocatalysis and biomedical applications other than sensing have been pursued with these systems. Interestingly, CNMs have also been envisaged as enzyme mimics, inhibitors, or detectors. We will concisely cover the progress made over the last five years on all these topics in the following sections. A plethora of works describe the use of CNMs as nanozymes, meaning nanostructures that mimic enzymes as they display catalytic activity [289] . Research in this area is intended to overcome some of the common limitations of enzymes, particularly, the limited physico-chemical resistance against solvents and changes in temperature, pH or other experimental conditions [290] . Potential applications range from various biomedical applications [291] , including innovative therapy [292] biosensing [293, 294] , and disinfection [295] , to environmental monitoring and remediation [296] . In particular, peroxidase mimicry by CNMs ( Figure 4 ) has been widely studied [297] , especially for the development of glucose biosensors [298] , although hydrolase mimicry is also attracting increasing interest [299] . A plethora of works describe the use of CNMs as nanozymes, meaning nanostructures that mimic enzymes as they display catalytic activity [289] . Research in this area is intended to overcome some of the common limitations of enzymes, particularly, the limited physico-chemical resistance against solvents and changes in temperature, pH or other experimental conditions [290] . Potential applications range from various biomedical applications [291] , including innovative therapy [292] biosensing [293, 294] , and disinfection [295] , to environmental monitoring and remediation [296] . In particular, peroxidase mimicry by CNMs (Figure 4 ) has been widely studied [297] , especially for the development of glucose biosensors [298] , although hydrolase mimicry is also attracting increasing interest [299] . . CNMs typically used for peroxidase mimicry (left) and a possible reaction mechanism that ultimately generates hydroxyl radicals for the oxidation of colorless 3,3 ,5,5 -tetramethylbenzidine (TMB) to a colored product (oxTMB). Reprinted with permission from [300] , Copyright © 2022, American Chemical Society. In particular, CNDs have been functionalized with Fe (III) to mimic peroxidases and exert antimicrobial activity through generation of hydroxyl radicals [301] . In contrast, no hydroxyl radicals were generated when they were derivatized with glucose or cyclodextrin to mimic peroxidases, indicating a different mechanism [302] . The peroxidase mimicry activity can be correlated to the phosphorescence quantum yield and can inhibit bacterial growth under light irradiation, an activity that was envisaged for photodynamic antimicrobial chemotherapy applications [303] . Alternatively, the use of light could trigger radical oxygen species generation by the CND nanozymes, in an effort to mimic nuclease activity and cleave DNA [304] . Chemical functionalization has been successfully employed to attain CNDs with switchable fluorescence too. In this case, the fluorescence of amino-derivatized CNDs can be quenched by chelation with Fe(II) ions as nanozymes, and restored upon treatment with hydrogen peroxidase with a concomitant shift from yellow to green [305] . Furthermore, addition of other divalent metal cations can lead to additional advantages. For instance, Mn(II) extends the peroxidase mimicry by CNDs to neutral pH values, which is otherwise rather uncommon [306] . Despite the fact that mimicking enzymes' enantioselectivity is a grand challenge, recent reports are demonstrating it is possible, in topoisomerase mimicry, for example [307] . Heteroatom-doped CNDs have been developed for theranostics as well, thanks to nanozyme activity [308] . Many other examples of nanozymes based on CNDs have been reported, through addition of other components, such as hemin [309] , metal nanoparticles (NPs) [310, 311] , co-doping with various elements [312] [313] [314] , MOFs [315] , carbon nitride [316] , and metal oxides [317] . Both graphene oxide (GO) and its reduced derivative (rGO) have also demonstrated peroxidase mimicking ability, which has been ascribed to the presence of carbonyl groups on the surface of the nanomaterial that get activated by hydrogen peroxide as a key step in the catalytic cycle [318] . Interestingly, rGO co-doping with N and B allowed development of nanozymes for the selective mimicry of peroxidases (but not oxidases) with enhanced catalytic performance for the development of biosensors [319] . Analogously, oxidized CNTs demonstrated peroxidase-like activity, which was envisaged for the treatment of bacterial infections [320] . Different oxygen-bearing functional groups exert competing interactions with hydrogen peroxide (Figure 5 ), and thus control over oxidation is important [320] . Combination of CNTs with other chemical components is a popular strategy to tailor nanozyme activity to the intended application. In a recent example, SWCNTs have been functionalized with a nickel complex for the biomimicry of oxidase for H 2 oxidation, and subsequent integration in fuel cells [267] . Alternatively, MWCNTs were coated with polypyrrole to introduce N-based ligands for Fe to be used in single-atom catalysis as peroxidase mimics [321] . CNTs were combined with hemin for peroxidase mimicry also [322, 323] . They have been derivatized with polyoxometallatebased metal-organic frameworks (MOFs) for the selective sensing of cysteine [324] , or with copper complexes [325] , MOFs [326] , and NPs [327] to develop nanozymes. For this type of application, many types of metal NPs have been used [328] [329] [330] , as well as polymers to mimic phosphodiesterases [331] . Peroxidase mimicry can be exerted by other CNMs as well, and for various uses. CNHs have been used as peroxidase mimics for the detection of drug traces as environmental pollutants [340] . They have been combined with nanosized ceria to detect hydrogen peroxide in commodity products, such as washing liquids and milk [341] . In the case of CNOs, nitrogen doping has been successfully applied to improve their catalytic performance in the electrochemical generation of molecular oxygen from hydrogen peroxide [342] . Boron and nitrogen co-doped CNOs showed great performance as electrocatalysts for the oxygen reduction reaction [95] . Interestingly, in the case of NDs, they were envisaged for redox-enzyme mimicry, with an activity that could be selectively tailored depending on the pH. At acidic pH, NDs catalyzed the reduction of molecular oxygen and hydrogen peroxide. At alkaline pH, they catalyzed the dismutation decomposition of hydrogen peroxide to produce molecular oxygen. It was proposed that the molecular mechanism of their peroxidase-like activity is electron-transfer acceleration, the source of which is likely derived from oxygen-containing functional groups on their surface [343] . Finally, besides peroxidases, and, generally, redox-active enzymes, which represent the vast majority of nanozyme mimicry studies on CNMs, hydrolases have started to attract scientists' attention. In a recent report, fullerene derivatives were applied to this end through the presentation of multiple functional groups inspired from the natural enzymes' catalytic sites [344] . Analogously to the other CNMs, fullerenes could also act as peroxidase mimics at acidic pH, and were thus envisaged for the eradication of Helycobacter pylori in vivo [345] . CNTs can be further assembled into macroscopic materials, such as carbon nanofibers (CNFs), which find many uses, especially in high-performance composites and energy devices [332] [333] [334] [335] [336] . In this case, they have been decorated with Fe(III) complexes to mimic oxidases [337] , peroxidases, and catalases for sensing and environmental technology [338] . Analogously to CNTs, CNFs can be oxidized, although gas-phase methods are preferable to the liquid-phase methods typically used for CNTs, to preserve the CNF macroscopic morphology, with the additional advantage of being virtually waste-free [339] . Peroxidase mimicry can be exerted by other CNMs as well, and for various uses. CNHs have been used as peroxidase mimics for the detection of drug traces as environmental pollutants [340] . They have been combined with nanosized ceria to detect hydrogen peroxide in commodity products, such as washing liquids and milk [341] . In the case of CNOs, nitrogen doping has been successfully applied to improve their catalytic performance in the electrochemical generation of molecular oxygen from hydrogen peroxide [342] . Boron and nitrogen co-doped CNOs showed great performance as electrocatalysts for the oxygen reduction reaction [95] . Interestingly, in the case of NDs, they were envisaged for redox-enzyme mimicry, with an activity that could be selectively tailored depending on the pH. At acidic pH, NDs catalyzed the reduction of molecular oxygen and hydrogen peroxide. At alkaline pH, they catalyzed the dismutation decomposition of hydrogen peroxide to produce molecular oxygen. It was proposed that the molecular mechanism of their peroxidase-like activity is electron-transfer acceleration, the source of which is likely derived from oxygen-containing functional groups on their surface [343] . Finally, besides peroxidases, and, generally, redox-active enzymes, which represent the vast majority of nanozyme mimicry studies on CNMs, hydrolases have started to attract scientists' attention. In a recent report, fullerene derivatives were applied to this end through the presentation of multiple functional groups inspired from the natural enzymes' catalytic sites [344] . Analogously to the other CNMs, fullerenes could also act as peroxidase mimics at acidic pH, and were thus envisaged for the eradication of Helycobacter pylori in vivo [345] . Fullerene derivatives have been envisaged for the inhibition of a variety of enzymes, including recent examples of HIV-1 protease [346] , ribonuclease A [347] , glycosidases [347] , ubiquitin-activating enzyme 1 [348] , and acetylcholinesterase [349] . Their size, hydrophobic nature, and spherical morphology appear very suitable for hydrophobic interactions with lipophilic sites on the target enzymes ( Figure 6 ), whilst C 60 functionalization can add hydrophilic appendages for more specific interactions. CNDs have been used to inhibit tyrosinase for cosmetic and food applications, thanks to hydrophobic interactions between the CNDs and the enzymatic surface, as well as chelation by the CND COOH groups of the enzyme copper ions. Tyrosinase is involved in the browning process of fruits and vegetables, and its overexpression has been linked to skin pigmentation disorders and tumorigenesis. Therefore, its inhibition could find several useful applications [350] . Furthermore, CNDs were found to tune glucose oxidase activity, depending on their functionalization type [224] , and inhibit maltase, an effect that was envisaged as an innovative means to control physiological glucose levels [230] . Enzyme inhibition has been studied for CNTs also. SWCNTs demonstrated the ability to act as competitive inhibitors for proteases, such as chymotrypsin, thanks to hydro- CNDs have been used to inhibit tyrosinase for cosmetic and food applications, thanks to hydrophobic interactions between the CNDs and the enzymatic surface, as well as chelation by the CND COOH groups of the enzyme copper ions. Tyrosinase is involved in the browning process of fruits and vegetables, and its overexpression has been linked to skin pigmentation disorders and tumorigenesis. Therefore, its inhibition could find several useful applications [350] . Furthermore, CNDs were found to tune glucose oxidase activity, depending on their functionalization type [224] , and inhibit maltase, an effect that was envisaged as an innovative means to control physiological glucose levels [230] . Enzyme inhibition has been studied for CNTs also. SWCNTs demonstrated the ability to act as competitive inhibitors for proteases, such as chymotrypsin, thanks to hydrophobic interactions between the curved CNT surface and a morphologically complementary crevice on the enzyme surface, without alteration of the enzyme secondary structure or active site [351] . CNMs can be engineered to monitor enzymatic activity. Several examples have been reported especially using CNDs, whose fluorescence is initially quenched through interaction with a second component, and then restored upon a chemical transformation triggered by the activity of the target enzyme [352] [353] [354] . To this end, graphene CNDs have been functionalized with a cobalt derivative to allow for redox-dependent fluorescence that can be used to detect alkaline phosphatase activity, in serum, through the dephosphorylation of a substrate on the CNDs that releases ascorbic acid, which restores fluorescence [352] . Through a similar principle, silver NPs have been applied to quench the fluorescence of CNDs, so that, in the presence of enzymatic activity that generates hydrogen peroxide as a byproduct (e.g., through an oxidase), the silver NP structure decomposes, and fluorescence is restored. Applications in the health sector were envisaged, in particular for the monitoring of relevant biomolecules, such as glucose or cholesterol that could act as substrates for the corresponding oxidase [353] . Alternatively, glycosidases could be monitored through a similar principle, by functionalizing the CNDs to favor interaction with p-nitrophenol, which is generated through enzymatic activity on a glycosylated derivative [354, 355] . Another target enzyme was thioredoxin reductase, overexpressed in many cancer cells [356] . SWCNTs have been applied to enzyme biosensing. Recently, SWCNTs were coated with a peptide to develop a biosensor for trypsin detection in urine samples, exploiting variations in CNT near-infrared photoluminescence upon enzymatic degradation of the peptide coating [357] . In another example, CNTs were envisaged for applications in cancer diagnostics, through the detection of matrix metalloproteinase-7, which is overexpressed in cancer cells [358] . Finally, CNT-fibers have been used to develop highly sensitive (54 µA·cm −2 ·mM −1 ) photoelectrodes for the detection of NADH, which is a key cofactor in many biocatalytic processes; its quantification correlates to specific enzyme activity [359] . Biosensors typically comprise three elements, which are: (1) an element for biological recognition, such as an enzyme; (2) a transducer, to convert energy from the biorecognition event into another form (electrical, thermal, optical, etc.); (3) a signal processing system for the response readout and/or recording [360] . Biosensors often rely on enzyme inhibition, thus being ideal to monitor inhibitors that are relevant to human health, such as drugs or pollutants [361] . Enzymes are ideal components for biosensing, thanks to high sensitivity, specificity, low cost, and accessibility [360] . Coupling a semiconductor to enzymes can be exploited in photobiocatalysis, which is inspired by natural photosynthesis, but does not necessarily involve light for activation [362] . In general, inclusion of nanomaterials allows for better performance in a variety of analytical parameters, such as sensitivity, detection limit, stability, and response rate [363] . In particular, CNMs are ideal supports especially for biosensors that require multiple layers of enzymes, but also for providing a good electronic contact through the layers and with the electrodes [364] . CNMs can be good active supports for oxidoreductases as they may facilitate electron transfer to enhance catalysis, whilst offering a high surface area for high-level loading of enzymes [365] . However, the occurrence of direct electron transfer (DET) is a matter of ongoing debate, depending on the type of enzymes under consideration, the accessibility of their redox-active site to the CNMs, and the type of direct or indirect contact between CNMs and enzymes [265] . The electronic properties of CNMs render them attractive building blocks for electrochemical biosensors, besides the more traditional optical alternatives [366, 367] . Graphene is one of the most studied CNMs for a variety of biosensing devices (Figure 7 ) thanks to its exceptional electronic and mechanical properties, as recently reviewed in detail elsewhere [368] . Other less studied CNMs, such as CNOs, can also make attractive electrode components for the development of low-cost, simple to use, and highly sensitive sensors [237, 369] . CNOs (mean size of 30 nm) were employed as electrochemical sensors by covalently immobilizing the glucose oxidase enzyme (GOx) on their surface via carbodiimide chemistry. GOx selectively catalyzed the oxidation of glucose, giving a sensor with high sensitivity and selectivity. However, the catalytic activity of GOx on the sensor electrode was highly sensitive to environmental conditions such as temperature, pH and humidity. Furthermore, the performance of the sensor was limited by enzymatic stability. Thus, an enzyme-free glucose sensor was designed, using Pt-decorated CNOs (Pt@CNOs) that outperformed many other CNMs previously studied for the same application [237] . sensors [237, 369] . CNOs (mean size of 30 nm) were employed as electrochemical sensors by covalently immobilizing the glucose oxidase enzyme (GOx) on their surface via carbodiimide chemistry. GOx selectively catalyzed the oxidation of glucose, giving a sensor with high sensitivity and selectivity. However, the catalytic activity of GOx on the sensor electrode was highly sensitive to environmental conditions such as temperature, pH and humidity. Furthermore, the performance of the sensor was limited by enzymatic stability Thus, an enzyme-free glucose sensor was designed, using Pt-decorated CNOs (Pt@CNOs that outperformed many other CNMs previously studied for the same application [237] . In 2020, Cumba et al. [369] described the preparation of the first ink that was based on CNOs to produce cheap and disposable electrodes, yielding sensors with elevated performance (Figure 8) . Careful selection and optimization of all the components was a key step to attain a suitable formulation for the ink to be screen-printed. They included the In 2020, Cumba et al. [369] described the preparation of the first ink that was based on CNOs to produce cheap and disposable electrodes, yielding sensors with elevated performance ( Figure 8 ). Careful selection and optimization of all the components was a key step to attain a suitable formulation for the ink to be screen-printed. They included the conducting nanocarbons (i.e., graphite (GRT) and CNOs), the polymer binder, the plasticizer, and the organic solvent. The electrodes were screen-printed and they consisted of a conducting network of interconnected CNMs with a uniform distribution. The system displayed a heterogeneous electron transfer rate constant corresponding to 1.3 ± 0.7 × 10 −3 cm·s −1 and also a current density that was higher than the ferrocene/ferrocenium coupled to a GRT screenprinted electrode that was commercially available. Furthermore, the CNO/GRT electrode allowed for the detection of dopamine in micromolar concentration (i.e., 10.0-99.9 µM), and with a 0.92 µM detection limit. The analytical sensitivity thus revealed a notable 4-fold increase relative to the commercial reference electrode based on GRT. Overall, this study opened the way to the use of CNO-based electrodes for high-performance sensing, electrocatalysis and battery research [369] . As can be seen from Table 1 , the vast majority of CNM-enzyme conjugates have be studied for biosensing applications. The most popular target molecule is glucose for bi metric health monitoring (Table 2) [224, 227, 228, 237, 249, 269, 271, 273] . However, biosenso have been developed to detect many other bioactive compounds too, such as cholester [312, 370, 371] and triglycerides [282] , lactose [220] and lactate [225, 280] , neurotransmitte [234, 240, 246, 278, 279, 372] and hormones [239] , various disease biomarkers [244, 257, 26 microRNAs [223] , drugs [218, 287] , pathogens [219] and toxins [221] , xanthine [262] an caffeic acid [373] , p-coumaric acid [232] , ferulic acid [233] , trace metals [274] , and oxyg [268] . As can be seen from Table 1 , the vast majority of CNM-enzyme conjugates have been studied for biosensing applications. The most popular target molecule is glucose for biometric health monitoring (Table 2) [224, 227, 228, 237, 249, 269, 271, 273] . However, biosensors have been developed to detect many other bioactive compounds too, such as cholesterol [312, 370, 371] and triglycerides [282] , lactose [220] and lactate [225, 280] , neurotransmitters [234, 240, 246, 278, 279, 372] and hormones [239] , various disease biomarkers [244, 257, 261] , microRNAs [223] , drugs [218, 287] , pathogens [219] and toxins [221] , xanthine [262] and caffeic acid [373] , p-coumaric acid [232] , ferulic acid [233] , trace metals [274] , and oxygen [268] . Biofuel cells are electrochemical devices that typically use redox enzymes as sustainable catalysts for the conversion of chemical energy into electrical energy ( Figure 9 ); they consist of two-electrode cells that are separated by a proton-conducting medium. At the bioanode, fuels are oxidized, freeing electrons that flow to the biocathode through the external electrical circuit. At the biocathode, oxidants such as oxygen or peroxide are reduced to water [374] . Redox-active enzymes have attracted great interest for their use in the electrochemical production of fuels as sustainable alternatives in the field of clean energy, such as water splitting reactions [375] . the electrochemical production of fuels as sustainable alternatives in the field of clean energy, such as water splitting reactions [375] . Conjugation with CNMs allows for high-performance devices. They have been coupled to enzymes to serve as anodes [248, 251, 258, 259, 269, 285] , cathodes [253, 267, 276, 277, 286] , or both [247, 284] . An electrochemical reaction of particular interest is the molecular oxygen reduction (ORR) at the cathode. In this case, use of CNT-laccase as biocathode allowed reaching current densities >1.8 mA·cm −2 , a direct electron transfer efficiency as high as 70-100%, and a turnover frequency of 5.0·10 3 s −1 [253] . When bilirubin oxidase was used coupled to CNTs at the cathode, a maximum current density of 5.5 mA·cm −2 was found, and a power density of 1.85 mW·cm −2 at 0.6 V was attained, relative to 2.46 mW·cm −2 at 0.32 V with Pt/C as counter electrode [267] . Addition of catalase to a glucose oxidase (GOx)-CNT conjugate Conjugation with CNMs allows for high-performance devices. They have been coupled to enzymes to serve as anodes [248, 251, 258, 259, 269, 285] , cathodes [253, 267, 276, 277, 286] , or both [247, 284] . An electrochemical reaction of particular interest is the molecular oxygen reduction (ORR) at the cathode. In this case, use of CNT-laccase as biocathode allowed reaching current densities >1.8 mA·cm −2 , a direct electron transfer efficiency as high as 70-100%, and a turnover frequency of 5.0·10 3 s −1 [253] . When bilirubin oxidase was used coupled to CNTs at the cathode, a maximum current density of 5.5 mA·cm −2 was found, and a power density of 1.85 mW·cm −2 at 0.6 V was attained, relative to 2.46 mW·cm −2 at 0.32 V with Pt/C as counter electrode [267] . Addition of catalase to a glucose oxidase (GOx)-CNT conjugate was thought to be another convenient strategy for ORR. In this case, GOx catalyzes the oxidation of glucose to gluconolactone with the concomitant consumption of molecular oxygen to produce hydrogen peroxide, which is then converted by the catalase into water and molecular oxygen that feeds back into the GOx reaction. As a result, this type of catalyst reached a maximum power density of 0.18 mW·cm −2 and a current density of 59 µA·cm −2 [276] . Another additive that can assist with catalytic performance in ORR is 2,2 -azino-di-(3-ethylbenzthiazoline sulfonic acid) or ABTS, which is a common substrate for hydrogen peroxidase and acts as an efficient electron transfer mediator between the enzyme and the electrode surface. With ABTS, a maximum power density of 1.12 mW·cm −2 at 0.45 V was obtained, which after two weeks had decreased just to 0.928 mW·cm −2 , indicating good stability over time [277] . Wearable CNT-based biofuel cells were developed on a cotton textile that allowed illumination of an LED on the cloth [376] . Amongst the CNMs that have been used with enzymes in biofuel cells as summarized in Table 1 , CNTs are certainly the mostly studied [247, 248, 251, 253, 258, 259, 267, 269, 276, 277, [284] [285] [286] . Recently, scientists are recognizing innovation opportunities also in other types of CNMs, such as CNDs [229] , GO [242] or rGO [275] , although reports in this direction are still very limited. Thanks to great progress on biotechnology and protein engineering, biocatalysis has emerged as a green solution to increase the efficiency of industrial processes in a sustainable way [377] . Its importance and societal impact has been recognized through the Nobel Prize in chemistry in 2018 to Arnold, who pioneered the directed evolution that enabled development of resistant enzymes of industrial interest [378] . CNMs can be envisaged as active supports to immobilize enzymes and facilitate their recycling [379] . Besides, their electronic properties may favor the catalytic performance of redox-active enzymes. To this end, enzymes have been coupled to CNTs to enable asymmetric hydrogenation in flow [380] . Furthermore, bioelectrocatalysis involving direct electron transfer (DET) can benefit from the use of CNMs as active supports for redox enzymes, and the role played by their surface functionalization in the process has recently been reviewed [381] . Enzymes supported on nanomaterials can be very convenient to detect pollutants for environmental monitoring through the development of sensitive sensors, but also for their removal from polluted waters [382] . For example, CNMs coupled to enzymes can be applied for the electrochemical monitoring of chromium [383] . CNDs' fluorescence has also been envisaged for the optical detection of organic pesticides through coupling with an enzymatic reaction [384] . In addition, rGO has been envisaged for the detection of pesticides through the immobilization of an esterase on a biocomposite containing fibrin and thrombin, which was assembled taking inspiration form the blood coagulation process [245] . Finally, CNOs were coupled to a peroxidase in a cyclodextrin polymer matrix for the detection of herbicides, as tested in soil and river water samples [238] . The rise of smart materials that can respond and adapt to stimuli and changes in the local microenvironment has opened new avenues that are enabling great progress especially in the biomedical field [385] . Enzymes can be used as convenient stimuli for the design of responsive materials [386] , with great potential in the development of combined therapy and diagnosis, for instance through activation on a target pathological site characterized by the selective overexpression of certain enzymes [387] . The coupling of enzyme-responsive materials with nanostructures can be convenient to develop photodynamic therapies for cancer treatment [388] . Alternatively, enzymes can be supported onto CNMs for combined chemodynamic therapy (CDT). For example, MWCNTs were functionalized with Fe 3 O 4 and glucose oxidase, so that the enzyme could convert glucose into gluconate and hydrogen peroxide. Conversion of the latter through the iron oxide-mediated Fenton reaction into hydroxyl radicals induces tumor cell death, and the reaction is favored by the lowered pH of the local microenvironment due to gluconate production. Finally, near-infrared (NIR) light irradiation can further boost the overall process at the target pathological site through generation of hyperthermia [252] . With the rise of biologics, enzymes have found applications also as therapeutic agents. As an example, laronidase can be used as replacement therapy for a type of mucopolysaccharidosis that is associated with deficiency of the natural enzyme, which hydrolyses glucosaminoglycans, causing their pathological accumulation in lysosomes. MWCNTs were thus envisaged as vectors for laronidase, which was covalently conjugated onto the CNMs [254] . There are clearly many unexplored opportunities in this research area that are worth future investigation. The possibility of biodegrading CNMs through enzymatic activity is very appealing for various reasons, including lowering their persistence in the environment after use, but also avoiding or reducing their bioaccumulation in living organisms. Furthermore, the breaking down of larger CNMs, such as GO, into smaller components, can be envisaged as a green production method of graphene quantum dots ( Figure 10 ) [389] . The possibility of biodegrading CNMs through enzymatic activity is very appealing for various reasons, including lowering their persistence in the environment after use, but also avoiding or reducing their bioaccumulation in living organisms. Furthermore, the breaking down of larger CNMs, such as GO, into smaller components, can be envisaged as a green production method of graphene quantum dots ( Figure 10 ) [389] . In general, the aromatic nature of CNTs renders them persistent in the environment, with little or no degradation by microorganisms [390] , yet their oxidized forms appear to be biodegradable by microorganisms, whose enzymes are likely to use hydroxyl groups on the CNT surface as attackable sites that can be processed through enzymatic activity [391] . Various peroxidases have been found to be able to biodegrade CNTs and G derivatives, as recently reviewed [392] . They are mainly horseradish peroxidase (HRP), myeloperoxidase (MPO), manganese peroxidase (MnP) and lignine peroxidase (LiP). These four enzymes require hydrogen peroxide to participate in the degradation of CNMs. In the enzymatic degradation process of CNMs, molecular docking technology is used to predict possible binding sites, which helps to understand the degradation mechanism [393] . Recently, oxidases were reported to biodegrade MWCNTs [394] , CNDs [8, 395] , and fullerenes [396] . It is not surprising to see that nanozymes are being developed for the same purpose, for instance as applied to the degradation of GO [397] . It is worth noting that besides the type of CNM, the level and type of functionalization is one of the factors playing a key role in determining the CNM biodegradation. Whilst it is accepted that oxidation generally favors biodegradation [150] , other types of functionalization can have the opposite effect. In particular, chemical reduction of GO [398] and/or coating with bovine serum albumin or polyethylene glycol [399] rendered the CNM resistant to peroxidase-mediated biodegradation. CNM biodegradation mediated by bacteria typically involves electron-transfer pro- Figure 10 . Enzymatic biodegradation of GO as a green production method of graphene quantum dots. Reproduced with permission from [389] , Copyright © 2022, American Chemical Society. In general, the aromatic nature of CNTs renders them persistent in the environment, with little or no degradation by microorganisms [390] , yet their oxidized forms appear to be biodegradable by microorganisms, whose enzymes are likely to use hydroxyl groups on the CNT surface as attackable sites that can be processed through enzymatic activity [391] . Various peroxidases have been found to be able to biodegrade CNTs and G derivatives, as recently reviewed [392] . They are mainly horseradish peroxidase (HRP), myeloperoxidase (MPO), manganese peroxidase (MnP) and lignine peroxidase (LiP). These four enzymes require hydrogen peroxide to participate in the degradation of CNMs. In the enzymatic degradation process of CNMs, molecular docking technology is used to predict possible binding sites, which helps to understand the degradation mechanism [393] . Recently, oxidases were reported to biodegrade MWCNTs [394] , CNDs [8, 395] , and fullerenes [396] . It is not surprising to see that nanozymes are being developed for the same purpose, for instance as applied to the degradation of GO [397] . It is worth noting that besides the type of CNM, the level and type of functionalization is one of the factors playing a key role in determining the CNM biodegradation. Whilst it is accepted that oxidation generally favors biodegradation [150] , other types of functionalization can have the opposite effect. In particular, chemical reduction of GO [398] and/or coating with bovine serum albumin or polyethylene glycol [399] rendered the CNM resistant to peroxidase-mediated biodegradation. CNM biodegradation mediated by bacteria typically involves electron-transfer processes, which lead to the breaking of C-C covalent bonds. As a result, numerous pores arise on the surface of CNMs which lose structural integrity. Electrons can flow in either direction at the CNM-bacteria interface. In particular, cationic and anionic CNMs act as electron acceptors and donors, respectively [400] . Furthermore, oxygen interference can occur at the point of electron transfer between bacteria and CNMs [401] . In general, the functionalization of CNMs with anionic species on the surface of CNMs favors the electrostatic interaction with enzymes, which often display cationic amino acids on their surface, but also the catalytically-active heme group in redox-active enzymes plays a role in the interaction with CNMs. Clearly, pristine CNMs may be more challenging to degrade, and defect sites offer typical locations for the beginning of their structural deterioration [402] . Currently, fullerene biodegradation is still a largely unexplored research topic. It is known that this nanocarbon is challenging to degrade when exposed to soil bacteria [403] . However, the situation is notably improved in the case of organics-rich clay, such that more than half of the fullerene present can be mineralized just over two months, and even more so in the case of functionalized fullerol. Its structural deterioration can be notably accelerated through the combination of biodegradation with photochemistry, which likely mediates the destruction of the stable aromatic core [404] . Likewise, C 60 photodegradation using UV light was facilitated by hydroxylation [405] . In another study, fullerene aggregates decreased in volume upon exposure to bacteria, with occurrence of hydroxylation, although the structural deterioration of the nanocarbon was slow and no significant production of carbon dioxide from C 60 was noted, using isotope labelling [406] . In general, the efficiency of photodegradation can be relatively high, but it should be noted that only UV light can degrade CNMs. In natural environments, CNMs will react with other substances too, and their degradation by UV light will be affected by all these factors. There is still a knowledge gap in the detailed understanding of biodegradation of several CNMs, especially in realistic experimental conditions pertaining to those found in the environment, including soil and water. Combining CNMs and enzymes requires a diverse skill set that is rare to find and represents a multidisciplinary research area that bears many technical and scientific challenges. However, a growing number of scientists are trying to innovate in this exciting field. The focus of our review has been to provide a concise overview from which it is evident how most studies have been focused on CNTs and, more recently, on graphene-based materials and CNDs, for applications in biosensing and biofuel cells. Nonetheless, CNMs offer far more benefits, and the multivarious members of the nanocarbon family still present today a valuable innovation opportunity that is worth exploring. Among other aspects that deserve further examination is their environmental fate, especially how biodegradation and photodegradation processes can improve the efficiency of CNM degradation. Further research potential can be found in the development of computational methods to enhance enzymatic performance and robustness [407] , including machine learning for enzyme engineering [408] , potentially coupled to directed evolution approaches [409] . The range of enzymatic activity can be further expanded through the incorporation of unnatural amino acids [410] , thanks to the emergence of robust methods for their genetic encoding [411] . Higher levels of complexity for the development of the next-generation devices can be attained with the incorporation of multienzymatic cascade reactions [412] , also in confined environments [413] , in an attempt to mimic, or go even beyond, the mesmerizing performance of biochemical cascades in living organisms. To this end, advancing electrochemical techniques for the characterization of enzymes at the electrode interface will be key [414] , especially to leverage the unique electronic properties of CNMs and their application to further enhancing enzymatic activity. In particular, an attractive area is the development of wearable, flexible bioelectronics for the harvesting of bioenergy and its use in self-powered biosensing for health monitoring [415] . The Devil and Holy Water: Protein and Carbon Nanotube Hybrids Under the lens: Carbon nanotube and protein interaction at the nanoscale How do proteins 'response' to common carbon nanomaterials? Protein immobilization on graphene oxide or reduced graphene oxide surface and their applications: Influence over activity, structural and thermal stability of protein Advances in biotechnological synthetic applications of carbon nanostructured systems Biodegradation of single-walled carbon nanotubes in macrophages through respiratory burst modulation Biodegradation of carbon nanohorns in macrophage cells Enzyme-catalyzed biodegradation of carbon dots follows sequential oxidation in a time dependent manner Protein corona hinders N-CQDs oxidative potential and favors their application as nanobiocatalytic system Biological interactions of carbon-based nanomaterials: From coronation to degradation Corona exchange dynamics on carbon nanotubes by multiplexed fluorescence monitoring The winding road for carbon nanotubes in nanomedicine Carbon nanomaterials for electro-active structures: A review Flexible electrochemical bioelectronics: The rise of in situ bioanalysis Carbon nanomaterials: Synthesis, functionalization and sensing applications. Nanomaterials 2021, 11, 967 ExplorEnz-The Enzyme Database Carbon-based smart nanomaterials in biomedicine and neuroengineering Nanomaterials for cardiac tissue engineering Carbon nanotubes for organ regeneration: An electrifying performance Electrically conductive nanomaterials for cardiac tissue engineering Exploring the effectiveness of incorporating carbon nanotubes into bioengineered scaffolds to improve cardiomyocyte function Multifunctional conductive biomaterials as promising platforms for cardiac tissue engineering Electroconductive biomaterials for cardiac tissue engineering Integrating carbon nanomaterials with metals for bio-sensing applications Mix and match metal oxides and nanocarbons for new photocatalytic frontiers Metal-free photocatalysis: Two-dimensional nanomaterial connection toward advanced organic synthesis Into the carbon: A matter of core and shell in advanced electrocatalysis Noble-metal-free multicomponent nanointegration for sustainable energy conversion Carbon-based fibers for advanced electrochemical energy storage devices Carbon foams: 3D porous carbon materials holding immense potential Porous carbons: Structure-oriented design and versatile applications From molecular precursors to nanoparticles-Tailoring the adsorption properties of porous carbon materials by controlled chemical functionalization Tailoring polymer colloids derived porous carbon spheres based on specific chemical reactions Porous carbons derived from collagen-enriched biomass: Tailored design, synthesis, and application in electrochemical energy storage and conversion Rational design of tailored porous carbon-based materials for CO 2 capture Biomass derived porous carbon for CO 2 capture Nanoporous materials for the onboard storage of natural gas Biomass-derived porous carbon materials with different dimensions for supercapacitor electrodes: A review Block copolymer-based porous carbons for supercapacitors Tunable porous carbon spheres for high-performance rechargeable batteries Tailoring porous carbon spheres for supercapacitors Porous carbon nanosheets: Synthetic strategies and electrochemical energy related applications Porous carbon: A versatile material for catalysis Metal/porous carbon composites for heterogeneous catalysis: Old catalysts with improved performance promoted by N-doping Recent advances in functionalized micro and mesoporous carbon materials: Synthesis and applications The higher fullerenes: Isolation and characterization of C 76 , C 84 , C 90 , C 94 , and C 70 O, an oxide of D 5h -C 70 Fullerenes C 60 and C 70 in flames Solid C 60 : A new form of carbon 07-Functionalized fullerenes: Synthesis and functions Heterofullerenes: Doped buckyballs. In Chemical Synthesis and Applications of Graphene and Carbon Materials Endohedral fullerenes: Synthesis, isolation, mono-and bis-functionalization Noble gas endohedral fullerenes A fresh mechanism for how buckyballs form in space Fullerene-based delivery systems Multivalent glycosylated nanostructures to inhibit ebola virus infection Biomedical engineers get to revisit an old friend. Mater. Today The pharmaceutical multi-activity of metallofullerenol invigorates cancer therapy Fullerenes: The stars of photovoltaics Fullerene-based materials for photovoltaic applications: Toward efficient, hysteresis-free, and stable perovskite solar cells Carbon nano-onions for bioimaging and cancer therapy applications Reactivity differences between carbon nano onions (CNOs) prepared by different methods Carbon nano-onions in biomedical applications: Promising theranostic agents Far-red fluorescent carbon nano-onions as a biocompatible platform for cellular imaging Review: Carbon onions for electrochemical energy storage Boron/nitrogen-codoped carbon nano-onion electrocatalysts for the oxygen reduction reaction Impact of carbon nano-onions on Hydra vulgaris as a model organism for nanoecotoxicology Carbon nano-onions as non-cytotoxic carriers for cellular uptake of glycopeptides and proteins Carbon nano-onions as fluorescent on/off modulated nanoprobes for diagnostics Supramolecular functionalization of carbon nano-onions with hyaluronic acid-phospholipid conjugates for selective targeting of cancer cells Carbon nano-onions (multi-layer fullerenes): Chemistry and applications Functionalization of multilayer fullerenes (carbon nano-onions) using diazonium compounds and "click" chemistry Non-covalent functionalization of carbon nano-onions with pyrene-BODIPY dyads for biological imaging Highly surface functionalized carbon nano-onions for bright light bioimaging White-light-emitting carbon nano-onions: A tunable multichannel fluorescent nanoprobe for glutathione-responsive bioimaging Graphene structure in carbon nanocones and nanodiscs Nano-aggregates of single-walled graphitic carbon nano-horns Buffer gas optimization in CO 2 laser ablation for structure control of single-wall carbon nanohorn aggregates Structure, synthesis, and sensing applications of single-walled carbon nanohorns Single-walled carbon nanohorns as promising nanotube-derived delivery systems to treat cancer Carbon nanohorn-based electrocatalysts for energy conversion N-doped graphitized carbon nanohorns as a forefront electrocatalyst in highly selective O 2 reduction to H 2 O 2 Highly efficient hydrogen production through ethanol photoreforming by a carbon nanocone/Pd@TiO 2 hybrid catalyst Pd@TiO 2 /carbon nanohorn electrocatalysts: Reversible CO 2 hydrogenation to formic acid Carbon dots: A new type of carbon-based nanomaterial with wide applications Carbon dots for in vivo bioimaging and theranostics Carbon dots: Synthesis, formation mechanism, fluorescence origin and sensing applications Recent advances in synthesis, optical properties, and biomedical applications of carbon dots Dispersibility of carbon dots in aqueous and/or organic solvents Sustainable carbon-dots: Recent advances in green carbon dots for sensing and bioimaging Natural-product-derived carbon dots: From natural products to functional materials Recent development in synthesis of carbon dots from natural resources and their applications in biomedicine and multi-sensing platform A review of carbon dots produced from biomass wastes Long-wavelength, multicolor, and white-light emitting carbon-based dots: Achievements made, challenges remaining, and applications Influence of molecular fluorophores on the research field of chemically synthesized carbon dots Carbon Dots: A small conundrum The elusive nature of carbon nanodot fluorescence: An unconventional perspective The synthetic strategies, photoluminescence mechanisms and promising applications of carbon dots: Current state and future perspective Carbon dots as nano-organocatalysts for synthetic applications Carbon dots as photosensitisers for solar-driven catalysis Carbon dots for photocatalytic degradation of aqueous pollutants: Recent advancements Design and fabrication of carbon dots for energy conversion and storage Carbon nanodots for capacitor electrodes Chemical functionalization of nanodiamonds: Opportunities and challenges ahead Nanodiamond-based theranostic platform for drug delivery and bioimaging Nanodiamonds for advanced optical bioimaging and beyond A perspective on fluorescent nanodiamond bioimaging Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions Nanodiamond applications in skin preparations Emerging face of future nanotechnology Growing synergy of nanodiamonds in neurodegenerative interventions Nanodiamonds and their applications in cells Single particle tracking of fluorescent nanodiamonds in cells and organisms Nanodiamonds for in vivo applications Catalysis by hybrid sp 2 /sp 3 nanodiamonds and their role in the design of advanced nanocarbon materials Single-shell carbon nanotubes of 1-nm diameter Helical microtubules of graphitic carbon Growth, properties, and applications of branched carbon nanostructures Understanding single-walled carbon nanotube growth for chirality controllable synthesis 3-Functionalization of carbon nanotubes Influence of oxygen-containing functional groups on the environmental properties, transformations, and toxicity of carbon nanotubes Chirality pure carbon nanotubes: Growth, sorting, and characterization Building a bridge for carbon nanotubes from nanoscale structure to macroscopic application Carbon nanotubes and related nanomaterials: Critical advances and challenges for synthesis toward mainstream commercial applications Application-driven carbon nanotube functional materials Dielectric elastomer actuators, neuromuscular interfaces, and foreign body response in artificial neuromuscular prostheses: A review of the literature for an in vivo application Artificial muscles: Mechanisms, applications, and challenges Toward nanobioelectronic medicine: Unlocking new applications using nanotechnology. WIREs Nanomed Advanced carbon for flexible and wearable electronics Carbon nanotubes as optical sensors in biomedicine Single-walled carbon nanotubes as optical probes for bio-sensing and imaging Carbon nanotube-based biomaterials for orthopaedic applications Advances in carbon nanotubeshydrogel hybrids in nanomedicine for therapeutics Overview of carbon nanotubes for biomedical applications Lopez-Larrubia, P. Carbon nanotubes in biomedicine Prospects of an electroactive carbon nanotube membrane toward environmental applications Laser-induced graphene and carbon nanotubes as conductive carbon-based materials in environmental technology Recent Advances in Applications of Sorted Single-Walled Carbon nanotubes Carbon nanotube-and graphene-based nanomaterials and applications in high-voltage supercapacitor: A review Krzyzewska, I. Carbon nanotube wind turbine blades: How Far are we today from laboratory tests to industrial implementation? ACS Appl Single-walled carbon nanotubes in emerging solar cells: Synthesis and electrode applications Roles of carbon nanotubes in novel energy storage devices Horizontal single-walled carbon nanotube arrays: Controlled synthesis, characterizations, and applications Chirality-enriched carbon nanotubes for next-generation computing Carbon-based materials for electrochemical reduction of CO 2 to C 2+ oxygenates: Recent progress and remaining challenges Applications of carbon nanotubes in oxygen electrocatalytic reactions Recent advances in carbon-based metal-free electrocatalysts Enter the tubes: Carbon nanotube endohedral catalysis. Catalysts Carbon Nanotube-based non-precious metal electrode catalysts for fuel cells, water splitting and zinc-air batteries Carbon-based catalysts for Fischer-Tropsch synthesis Classification framework for graphene-based materials Graphene oxide in aqueous and nonaqueous media: Dispersion behaviour and solution chemistry Chemical and electrochemical synthesis of graphene oxide-A generalized view Microwave reduction of graphene oxide Restoration of the graphitic structure by defect repair during the thermal reduction of graphene oxide Synthetic tailoring of graphene nanostructures with zigzag-edged topologies: Progress and perspectives Emerging bottom-up strategies for the synthesis of graphene nanoribbons and related structures Graphene-based materials: Synthesis, characterization, properties, and applications Mechanisms of mechanical reinforcement by graphene and carbon nanotubes in polymer nanocomposites 2D Materials for skin-mountable electronic devices Graphene hybrid structures for integrated and flexible optoelectronics Laser fabrication of graphene-based flexible electronics Flexible graphene-channel memory devices: A review Graphene-based nanomaterials for flexible and stretchable batteries Graphene's role in emerging trends of capacitive energy storage Hybridized graphene for supercapacitors: Beyond the limitation of pure graphene Compact energy storage enabled by graphenes: Challenges, strategies and progress Planar graphene-based microsupercapacitors Heteroatom doped graphene engineering for energy storage and conversion Graphene-based membranes for water and wastewater treatment: A review Cation-π interactions in graphene-containing systems for water treatment and beyond Graphene-based carbocatalysts for carbon-carbon bond formation Three-dimensional graphene-based macrostructures for electrocatalysis Design, fabrication, and mechanism of nitrogen-doped graphene-based photocatalyst Theoretical understandings of graphene-based metal single-atom catalysts: Stability and catalytic performance Graphene: A disruptive opportunity for COVID-19 and future pandemics? Graphene-based scaffolds for regenerative medicine Ultrasensitive Field-Effect Biosensors Enabled by the Unique Electronic Properties of Graphene Graphene-based wearable piezoresistive physical sensors Large-scale syntheses of 2-D Materials: Flash joule heating and other methods Ultrafast, low-cost, and mass production of high-quality graphene Graphene standardization: The lesson from the East Smart hydrogels meet carbon nanomaterials for new frontiers in medicine Carbon nanotubes: Current perspectives on diverse applications in targeted drug delivery and therapies. Materials Biocompatibility and carcinogenicity of carbon nanotubes as biomaterials Toxicity of carbon nanotubes: Molecular mechanisms, signaling cascades, and remedies in biomedical applications Banning carbon nanotubes would be scientifically unjustified and damaging to innovation A facile approach to hydrophilic oxidized fullerenes and their derivatives as cytotoxic agents and supports for nanobiocatalytic systems Amperometric tyrosinase biosensors modified by nanomaterials of different nature for determining diclofenac Amperometric DNA biosensor for Mycobacterium tuberculosis detection using flower-like carbon nanotubes-polyaniline nanohybrid and enzyme-assisted signal amplification strategy Conjugation of carbon dots with β-galactosidase enzyme: Surface chemistry and use in biosensing QPRTase modified N-doped carbon quantum dots: A fluorescent bioprobe for selective detection of neurotoxin quinolinic acid in human serum Novel biocatalytic systems for maintaining the nucleotide balance based on adenylate kinase immobilized on carbon nanostructures A novel electrochemiluminescence biosensor for the detection of microRNAs based on a DNA functionalized nitrogen doped carbon quantum dots as signal enhancers Chiral control of carbon dots via surface modification for tuning the enzymatic activity of glucose oxidase Enhanced performance of reagent-less carbon nanodots based enzyme electrochemical biosensors Biodegradable poly(γ-glutamic acid)@glucose oxidase@carbon dot nanoparticles for simultaneous multimodal imaging and synergetic cancer therapy Label free glucose electrochemical biosensor based on poly(3,4-ethylenedioxy thiophene): Polystyrene sulfonate/titanium carbide/graphene quantum dots Carbon-dot-based ratiometric fluorescence glucose biosensor Methanol/oxygen enzymatic biofuel cell using laccase and NAD+-dependent dehydrogenase cascades as biocatalysts on carbon nanodots electrodes Maltase decorated by chiral carbon dots with inhibited enzyme activity for glucose level control Biocatalytic C=C bond reduction through carbon nanodot-sensitized regeneration of NADH analogues Development of a novel electrochemical biosensor based on carbon nanofibers-cobalt phthalocyaninelaccase for the detection of p-coumaric acid in phytoproducts Development of a novel electrochemical biosensor based on carbon nanofibers-gold nanoparticlestyrosinase for the detection of ferulic acid in cosmetics Carbon nanohorn modified platinum electrodes for improved immobilisation of enzyme in the design of glutamate biosensors Highly sensitive electrochemiluminescent immunoassay for neuron-specific enolase amplified by single-walled carbon nanohorns and enzymatic biocatalytic precipitation Preparation and characterization of alkaline phosphatase, horseradish peroxidase, and glucose oxidase conjugates with carboxylated carbon nano-onions Enzymatic and non-enzymatic electrochemical glucose sensor based on carbon nano-onions Carbon nano-onion peroxidase composite biosensor for electrochemical detection of 2,4-D and 2,4,5-T Decoration of reduced graphene oxide with rhodium nanoparticles for the design of a sensitive electrochemical enzyme biosensor for 17β-estradiol Hyphenation of enzyme/graphene oxide-ionic liquid/glassy carbon biosensors with anodic differential pulse stripping voltammetry for reliable determination of choline and acetylcholine in human serum Influence of three commercial graphene derivatives on the catalytic properties of a lactobacillus plantarum α-L-rhamnosidase when used as immobilization matrices Graphene oxide-supported carbon nanofiber-like network derived from polyaniline: A novel composite for enhanced glucose oxidase bioelectrode performance Development of effective lipase-hybrid nanoflowers enriched with carbon and magnetic nanomaterials for biocatalytic transformations Electrochemical immunosensor based on chitosan-gold nanoparticle/carbon nanotube as a platform and lactate oxidase as a label for detection of CA125 oncomarker Bioinspired assembly of reduced graphene oxide by fibrin fiber to prepare multi-functional conductive bionanocomposites as versatile electrochemical platforms A novel sensitive amperometric choline biosensor based on multiwalled carbon nanotubes and gold nanoparticles New biocatalyst including a 4-nitrobenzoic acid mediator embedded by the cross-linking of chitosan and genipin and its use in an energy device Fabrication of enzyme-based coatings on intact multi-walled carbon nanotubes as highly effective electrodes in biofuel cells A smart tongue depressor-based biosensor for glucose Construction of flexible enzymatic electrode based on gradient hollow fiber membrane and multi-wall carbon tubes meshes Green synthesis of ZnO nanoparticles decorated on polyindole functionalized-MCNTs and used as anode material for enzymatic biofuel cell applications Mild hyperthermia-enhanced enzyme-mediated tumor cell chemodynamic therapy Efficiency of Site-specific clicked laccase-carbon nanotubes biocathodes towards O 2 reduction Carbon nanotubes as nanovectors for intracellular delivery of laronidase in Mucopolysaccharidosis type I Carbon nanotube filled with magnetic iron oxide and modified with polyamidoamine dendrimers for immobilizing lipase toward application in biodiesel production Immobilization of peroxidase on functionalized MWCNTs-buckypaper/polyvinyl alcohol nanocomposite membrane An electrochemical immunosensor for cardiac Troponin I using electrospun carboxylated multi-walled carbon nanotube-whiskered nanofibres Enzyme precipitate coating of pyranose oxidase on carbon nanotubes and their electrochemical applications Enzymatic fuel cells with an oxygen resistant variant of pyranose-2-oxidase as anode biocatalyst Tyrosinase-immobilized CNT based biosensor for highly-sensitive detection of phenolic compounds A 3D electrochemical biosensor based on Super-Aligned Carbon NanoTube array for point-of-care uric acid monitoring Amperometric biosensors based on carboxylated multiwalled carbon nanotubes-metal oxide nanoparticles-7,7,8,8-tetracyanoquinodimethane composite for the determination of xanthine Biologically friendly room temperature ionic liquids and nanomaterials for the development of innovative enzymatic biosensors Biologically friendly room temperature ionic liquids and nanomaterials for the development of innovative enzymatic biosensors: Part II Oxidases, carbon nanotubes, and direct electron transfer: A cautionary tale Enhancing enzyme immobilization on carbon nanotubes via metal-organic frameworks for large-substrate biocatalysis Carbon nanotube-supported bio-inspired nickel catalyst and its integration in hybrid hydrogen/air fuel cells Oxygen biosensor based on carbon nanotubes directly grown on graphitic substrate Dawson-type polyoxometalate nanoclusters confined in a carbon nanotube matrix as efficient redox mediators for enzymatic glucose biofuel cell anodes and glucose biosensors Bimetallic Fe/Mn metal-organic-frameworks and Au nanoparticles anchored carbon nanotubes as a peroxidaselike detection platform with increased active sites and enhanced electron transfer Facile one-step fabrication of glucose oxidase loaded polymeric nanoparticles decorating MWCNTs for constructing glucose biosensing platform: Structure matters Amperometric flow injection analysis of glucose using immobilized glucose oxidase on nano-composite carbon nanotubes-platinum nanoparticles carbon paste electrode An efficient flexible electrochemical glucose sensor based on carbon nanotubes/carbonized silk fabrics decorated with Pt microspheres Biotoxic trace metal ion detection by enzymatic inhibition of a glucose biosensor based on a poly(brilliant green)-deep eutectic solvent/carbon nanotube modified electrode Au NPs/N-doped CNTs supported on nickel foam as an anode for enzymatic biofuel cells Co-immobilization of glucose oxidase and catalase for enhancing the performance of a membraneless glucose biofuel cell operated under physiological conditions A novel three-dimensional carbonized PANI1600@CNTs network for enhanced enzymatic biofuel cell Highly sensitive amperometric detection of glutamate by glutamic oxidase immobilized Pt nanoparticle decorated multiwalled carbon nanotubes(MWCNTs)/polypyrrole composite Exploring the exocellular fungal biopolymer botryosphaeran for laccase-biosensor architecture and application to determine dopamine and spironolactone Microneedle-based biosensor for minimally-invasive lactate detection Immobilization of Candida antarctic lipase B on MWNTs modified by ionic liquids with different functional groups Development of an electrochemical biosensor for the determination of triglycerides in serum samples based on a lipase/magnetite-chitosan/copper oxide nanoparticles/multiwalled carbon nanotubes/pectin composite Highly active nanobiocatalyst from lipase noncovalently immobilized on multiwalled carbon nanotubes for baeyer-villiger synthesis of lactones Oriented immobilization of [NiFeSe] hydrogenases on covalently and noncovalently functionalized carbon nanotubes for H 2 /air enzymatic fuel cells Enhanced electrochemical oxidation of ethanol using a hybrid catalyst cascade architecture containing pyrene-TEMPO, oxalate decarboxylase and carboxylated multi-walled carbon nanotube Monofunctional pyrenes at carbon nanotube electrodes for direct electron transfer H 2 O 2 reduction with HRP and HRP-bacterial nanocellulose An enzyme-induced novel biosensor for the sensitive electrochemical determination of isoniazid Nanoreporter of an enzymatic suicide inactivation pathway Carbon-based nanozymes for biomedical applications Nanomaterials with enzyme-like characteristics (nanozymes): Next-generation artificial enzymes (II) Enzyme mimic nanomaterials and their biomedical applications Therapeutic applications of multifunctional nanozymes Nanozymes-Hitting the biosensing Functional nanomaterials with unique enzyme-like characteristics for sensing applications Biocatalytic nanomaterials: A new pathway for bacterial disinfection Carbon nanozymes: Enzymatic Properties, catalytic mechanism, and applications Recent advances in enzyme-free electrochemical hydrogen peroxide sensors based on carbon hybrid nanocomposites Peroxidase-Like activity of smart nanomaterials and their advanced application in colorimetric glucose biosensors Synthetic catalysts inspired by hydrolytic enzymes Progress and perspective on carbon-based nanozymes for peroxidase-like applications Electrochemical generation of Fe 3 C/N-doped graphitic carbon nanozyme for efficient wound healing in vivo Carbon dot nanozymes: How to be close to natural enzymes Phosphorescent carbon dots for highly efficient oxygen photosensitization and as photo-oxidative nanozymes Graphene oxide as a photocatalytic nuclease mimicking nanozyme for DNA cleavage Emission wavelength switchable carbon dots combined with biomimetic inorganic nanozymes for a two-photon fluorescence immunoassay Manganese as a catalytic mediator for photooxidation and breaking the pH limitation of nanozymes Chiral carbon dots mimicking topoisomerase I to mediate the topological rearrangement of supercoiled DNA enantioselectively Heteroatom doped carbon dots with nanoenzyme like properties as theranostic platforms for free radical scavenging, imaging, and chemotherapy Label-free and enzyme-free fluorescence detection of microRNA based on sulfydryl-functionalized carbon dots via target-initiated hemin/G-quadruplex-catalyzed oxidation The chain-like Au/carbon dots nanocomposites with peroxidase-like activity and their application for glucose detection In-situ reduction of Ag+ on black phosphorene and its NH2-MWCNT nanohybrid with high stability and dispersibility as nanozyme sensor for three ATP metabolites High-activity Mo, S co-doped carbon quantum dot nanozyme-based cascade colorimetric biosensor for sensitive detection of cholesterol -doped carbon quantum dots: Intrinsic peroxidase activity in a wide pH range and its antibacterial applications Zn dopants boost electron transfer of carbon dots for antioxidation Biomimetic sensor for ethambutol employing β-cyclodextrin mediated chiral copper metal organic framework and carbon nanofibers modified glassy carbon electrode Carbon dots/g-C3N4 nanoheterostructures-based signal-generation tags for photoelectrochemical immunoassay of cancer biomarkers coupling with copper nanoclusters Fe 3 O 4 /carbon nanodot hybrid nanoparticles for the indirect colorimetric detection of glutathione Origins of the peroxidase mimicking activities of graphene oxide from first principles A strong candidate to replace natural peroxidase in sensitive and selective bioassays Unraveling the enzymatic activity of oxygenated carbon nanotubes and their application in the treatment of bacterial infections Single-atom nanozyme based on nanoengineered Fe-N-C catalyst with superior peroxidase-like activity for ultrasensitive bioassays Biomimetic design for enhancing the peroxidase mimicking activity of hemin Peptide nucleic acid-assisted colorimetric detection of single-nucleotide polymorphisms based on the intrinsic peroxidase-like activity of hemin-carbon nanotube nanocomposites POMOF/SWNT nanocomposites with prominent peroxidasemimicking activity for L-cysteine "on-off switch" colorimetric biosensing Copper (II)-ploy-L-histidine functionalized multi walled carbon nanotubes as efficient mimetic enzyme for sensitive electrochemical detection of salvianic acid A Enzyme-free glucose sensor based on layer-by-layer electrodeposition of multilayer films of multi-walled carbon nanotubes and Cu-based metal framework modified glassy carbon electrode A dual-signal readout enzyme-free immunosensor based on hybridization chain reaction-assisted formation of copper nanoparticles for the detection of microcystin-LR Designing electrochemical interfaces based on nanohybrids of avidin functionalized-carbon nanotubes and ruthenium nanoparticles as peroxidase-like nanozyme with supramolecular recognition properties for site-specific anchoring of biotinylated residues Non-enzymatic electrochemical sensor based on sliver nanoparticle-decorated carbon nanotubes Platinum nanoparticle-deposited multi-walled carbon nanotubes as a NADH oxidase mimic: Characterization and applications A synthetic mimic of phosphodiesterase type 5 based on corona phase molecular recognition of single-walled carbon nanotubes A perspective on high-performance CNT fibres for structural composites Carbon fiber reinforced composites: Study of modification effect on weathering-induced ageing via nanoindentation and deep learning Comparative physical-mechanical properties assessment of tailored surface-treated carbon fibres Simultaneous improvements in conversion and properties of molecularly controlled CNT fibres Transparent and flexible high-power supercapacitors based on carbon nanotube fibre aerogels Fe 3 C/nitrogen-doped carbon nanofibers as highly efficient biocatalyst with oxidase-mimicking activity for colorimetric sensing Fe(III)-tannic acid complex derived Fe 3 C decorated carbon nanofibers for triple-enzyme mimetic activity and their biosensing application Gas-Phase functionalization of macroscopic carbon nanotube fiber assemblies: Reaction control, electrochemical properties, and use for flexible supercapacitors Electrochemical immunosensor based on Ag+-dependent CTAB-AuNPs for ultrasensitive detection of sulfamethazine H 2 O 2 sensing enhancement by mutual integration of single walled carbon nanohorns with metal oxide catalysts: The CeO 2 case Improvement of the structural and chemical properties of carbon nano-onions for electrocatalysis Nanodiamonds as pH-switchable oxidation and reduction catalysts with enzyme-like activities for immunoassay and antioxidant applications Fullerene-based mimics of biocatalysts show remarkable activity and modularity Fullerenol nanoparticles eradicate Helicobacter pylori via pH-responsive peroxidase activity Molecular dynamics simulation study of the HIV-1 protease inhibit ion using fullerene and new fullerene derivatives of carbon nanostructures Exploring the inhibitory and antioxidant effects of Fullerene and Fullerenol on Ribonuclease A Hydrophobic patch of Ubiquitin is important for its optimal activation by Ubiquitin activating enzyme E1 Competitive inhibition mechanism of acetylcholinesterase without catalytic active site interaction: Study on functionalized C 60 nanoparticles via in vitro and in silico assays Efficient tyrosinase nano-inhibitor based on carbon dots behaving as a gathering of hydrophobic cores and key chemical group Inhibition of α-chymotrypsin by pristine single-wall carbon nanotubes: Clogging up the active site Chemical redox modulated fluorescence of nitrogen-doped graphene quantum dots for probing the activity of alkaline phosphatase Yellow-emissive carbon dot-based optical sensing platforms: Cell imaging and analytical applications for biocatalytic reactions A universal fluorometric assay strategy for glycosidases based on functional carbon quantum dots: β-galactosidase activity detection in vitro and in living cells A reversible fluorescence nanoswitch based on dynamic covalent B-O bonds using functional carbon quantum dots and its application for α-glucosidase activity monitoring Carbon dot based, Naphthalimide coupled FRET pair for highly selective ratiometric detection of thioredoxin reductase and cancer screening A paper-based near-infrared optical biosensor for quantitative detection of protease activity using peptide-encapsulated SWCNTs Peptide decorated gold nanoparticle/carbon nanotube electrochemical sensor for ultrasensitive detection of matrix metalloproteinase-7 Photoelectrocatalytic detection of NADH on n-type silicon semiconductors facilitated by carbon nanotube fibers Immobilized enzymes in biosensor applications Recent advances in biosensors based on enzyme inhibition Photobiocatalysis: The power of combining photocatalysis and enzymes Advances in nanomaterial application in enzyme-based electrochemical biosensors: A review Trends in the layer-by-layer assembly of redox proteins and enzymes in bioelectrochemistry Developments in support materials for immobilization of oxidoreductases: A comprehensive review Carbon dots and graphene quantum dots in electrochemical biosensing Nanobioconjugates for signal amplification in electrochemical biosensing Graphene Biodevices for Early Disease Diagnosis Based on Biomarker Detection. ACS Sens. 2021 Electrochemical properties of screen-printed carbon nano-onion electrodes Au@carbon dot nanoconjugates as a dual mode enzyme-free sensing platform for cholesterol Colorimetric cholesterol sensor based on peroxidase like activity of zinc oxide nanoparticles incorporated carbon nanotubes Carbon Nanostructure Based Platform for Enzymatic Glutamate Biosensors Voltamperometric sensors and biosensors based on carbon nanomaterials used for detecting caffeic acid-A review Tackling the challenges of enzymatic (bio)fuel cells Enzyme electrochemistry for industrial energy applications-A perspective on future areas of focus Wearable high-powered biofuel cells using enzyme/carbon nanotube composite fibers on textile cloth State-of-the-art biocatalysis Navigating the unnatural reaction space: Directed evolution of heme proteins for selective Carbene and Nitrene transfer Controlling enzyme function through immobilization on graphene, graphene derivatives and other two dimensional nanomaterials H2-Driven biocatalytic hydrogenation in continuous flow using enzyme-modified carbon nanotube columns Rational surface modification of carbon nanomaterials for improved direct electron transfer-type bioelectrocatalysis of redox enzymes Nanomaterial-supported enzymes for water purification and monitoring in point-of-use water supply systems Recent advances in electrochemical monitoring of chromium Carbon dot-based bioplatform for dual colorimetric and fluorometric sensing of organophosphate pesticides The rise of intelligent matter Harnessing endogenous stimuli for responsive materials in theranostics Development of endogenous enzyme-responsive nanomaterials for theranostics Enzyme-assisted photodynamic therapy based on nanomaterials Composition and structure of fluorescent graphene quantum dots generated by enzymatic degradation of graphene oxide Environmental biodegradability of [14C] single-walled carbon nanotubes by Trametes versicolor and natural microbial cultures found in New Bedford Harbor sediment and aerated wastewater treatment plant sludge Degradation of multiwall carbon nanotubes by bacteria Biodegradation of carbon nanotubes, graphene, and their derivatives Application of molecular docking for the degradation of organic pollutants in the environmental remediation: A review Biodegradable multi-walled carbon nanotubes trigger anti-tumoral effects Enzymatic degradation of graphene quantum dots by human peroxidases Degradation of fullerene C 60 by human myeloperoxidase and some reaction products Peroxidase mimicking DNAzymes degrade graphene oxide The enzymatic oxidation of graphene oxide Surface coating-dependent cytotoxicity and degradation of graphene derivatives: Towards the design of non-toxic, degradable nano-graphene Oxidation and degradation of graphitic materials by naphthalene-degrading bacteria Reduction of graphene oxide via bacterial respiration Mechanistic investigations of horseradish peroxidase-catalyzed degradation of single-walled carbon nanotubes A. C 60 fullerene soil sorption, biodegradation, and plant uptake Degradation and microbial uptake of C 60 fullerols in contrasting agricultural soils Characterizing photochemical transformation of aqueous nC 60 under environmentally relevant Conditions Aging of fullerene C 60 nanoparticle suspensions in the presence of microbes Computational design of stable and soluble biocatalysts Machine learning in enzyme engineering Engineering new catalytic activities in enzymes Catalytic machinery of enzymes expanded Expanding the enzyme universe with genetically encoded unnatural amino acids Multienzymatic cascade reactions via enzyme complex by immobilization Biocatalytic cascades operating on macromolecular scaffolds and in confined environments Advancing techniques for investigating the enzyme-electrode interface On-body bioelectronics: Wearable biofuel cells for bioenergy harvesting and self-powered biosensing Acknowledgments: This article is based upon work from COST Action EsSENce CA19118, supported by COST (European Cooperation in Science and Technology). Available online: www.cost.eu (accessed on 15 December 2021). The authors wish to thank Michał Bartkowski for proofreading the manuscript. The authors declare no conflict of interest.