Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4

El-Sayed, Ramy; Bhattacharya, Kunal; Gu, Zhonglin; Yang, Zaixing; Weber, Jeffrey K.; Li, Hu; Leifer, Klaus; Zhao, Yichen; Toprak, Muhammet S.; Zhou, Ruhong; Fadeel, Bengt

doi:10.1038/srep21316

Cited by 44 publications

(28 citation statements)

References 45 publications

(63 reference statements)

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“…The interactions may induce changes in a protein conformation 45 or block an active site in an enzyme. 25 It was previously reported that SWCNT inhibited the most important of the isoenzymes, CYP3A4, mostly due to the occurrence of π-π stacking interactions between the nanotube walls and aromatic residues of the enzyme. 25 A carbon nanotube is, in fact, a rolled sheet of graphene, which is a single atomic layer of crystalline graphite; therefore, its surface consists of the same hexagonally arranged carbon atoms at sp 2 hybridization with π electrons.…”

Section: Discussionmentioning

confidence: 99%

“…Single-walled carbon nanotubes (SWCNT) inhibited the activity of the CYP3A4 enzyme by direct interaction between SWCNT and the enzyme. 25 Hitoshi et al reported that SWCNT also downregulated genes coding other CYP isoenzymes, namely, CYP1A1 and CYP1B1. 26 We turned our attention to other carbon nanostructures, such as diamond nanoparticles (DN), graphene oxide (GO) and graphite nanoparticles (GN), which were previously shown to be nontoxic or low toxic; however, no data are available on their potential interactions with CYP isoenzymes.…”

Section: Introductionmentioning

confidence: 99%

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Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells

Strojny¹,

Sawosz²,

Grodzik³

et al. 2018

IJN

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Introduction and objectiveCurrently, carbon nanostructures are vastly explored materials with potential for future employment in biomedicine. The possibility of employment of diamond nanoparticles (DN), graphene oxide (GO) or graphite nanoparticles (GN) for in vivo applications raises a question of their safety. Even though they do not induce a direct toxic effect, due to their unique properties, they can still interact with molecular pathways. The objective of this study was to assess if DN, GO and GN affect three isoforms of cytochrome P450 (CYP) enzymes, namely, CYP1A2, CYP2D6 and CYP3A4, expressed in the liver.MethodsDose-dependent effect of the DN, GO and GN nanostructures on the catalytic activity of CYPs was examined using microsome-based model. Cytotoxicity of DN, GO and GN, as well as the influence of the nanostructures on mRNA expression of CYP genes and CYP-associated receptor genes were studied in vitro using HepG2 and HepaRG cell lines.ResultsAll three nanostructures interacted with the CYP enzymes and inhibited their catalytic activity in microsomal-based models. CYP gene expression at the mRNA level was also downregulated in HepG2 and HepaRG cell lines. Among the three nanostructures, GO showed the most significant influence on the enzymes, while DN was the most inert.ConclusionOur findings revealed that DN, GO and GN might interfere with xenobiotic and drug metabolism in the liver by interactions with CYP isoenzymes responsible for the process. Such results should be considered if DN, GO and GN are used in medical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells

Strojny¹,

Sawosz²,

Grodzik³

et al. 2018

IJN

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“…On the other hand, it is well known that nanoparticles are rapidly coated with various proteins in biological fluids, forming a protein corona [20,21,22]. Therefore, some investigations have used bovine serum albumin (BSA), which is the most abundant protein in serum or plasma, as the dispersant for CNTs [23,24,25]. However, the abundance profile of proteins absorbed to CNTs did not match the protein profile of the serum [26].…”

Section: Introductionmentioning

confidence: 99%

The Dispersion State of Tangled Multi-Walled Carbon Nanotubes Affects Their Cytotoxicity

et al. 2016

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The medical applications of carbon nanotubes (CNTs) have garnered much attention. However, evaluating the safety of CNTs remains difficult, and no consensus has been reached. Moreover, assessing the biosafety of multi-walled CNTs (MWCNTs), which can become tangled during manufacturing, is challenging because they do not readily disperse. We studied how the dispersion state of tangled MWCNTs affects their cytotoxicity, using three sonicators. Flotube 9110 (FT9110), tangled MWCNTs, were dispersed in two dispersants (fetal bovine serum and polysorbate 80) using a new type of sonicator (PR-1) and two conventional sonicators. The size and cytotoxicity of the dispersed FT9110 were measured using the BEAS-2B human bronchial epithelial cell line. The PR-1 dispersed the FT9110 to agglomerates <200 nm in diameter; FT9110 dispersed with the PR-1 did not show cytotoxicity regardless of dispersant. The other sonicators dispersed the FT9110 to particles >1000 nm in diameter, and cytotoxicity depended on the dispersant. We found that excluding cells adhered to agglomerated FT9110 before evaluating cytotoxicity can lead to false-positive results. The PR-1 sonicator dispersed tangled FT9110 to many single fibers, which showed lower cytotoxicity than conventionally-sonicated MWCNTs. We suggest that dispersion state should be accounted for when evaluating the cytotoxicity of MWCNTs.

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“…For quantitative examination of surface mechanical properties, in particular the adhesion force defined as the difference between the maximum attractive force and the zero force, we utilized the peak force quantitative nanomechanical mapping (PF‐QNM) technique from which several surface mechanical properties can be extracted in real time . At a set‐point force of 600 nN, nontreated graphene exhibits an adhesion of ~40 nN, while a much stronger adhesion of ≈180 nN is observed for the material obtained after the photoreaction with IPA (Figure E,F).…”

mentioning

confidence: 99%

White‐Light Photoassisted Covalent Functionalization of Graphene Using 2‐Propanol

Lundstedt

Papadakis

et al. 2017

Small Methods

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of molecular species causes more subtle changes. [6,7] The edges of a graphene sheet are more reactive than the basal plane positions; hence, most covalent functionalizations are edge-selective. [8] In order to covalently functionalize the basal plane, more vigorous reaction conditions are generally required. Many of the presently used methods are via oxidation of graphite into graphene oxide using metal oxides and strong oxidizing acids. [9,10] Post-oxidation secondary functionalization of the introduced oxygen-containing functional groups [4,11] or reduction results in different types of modified graphene. The routes via graphene oxide result in defect-rich materials, where the type and extent of defects strongly depend on the initial oxidation method employed. [12,13] Alternative routes to covalently functionalized graphene employ various plasmas, atomic fluorine, or other radicals. [14][15][16][17][18][19][20][21][22] As is the case for the oxidation strategy, efficient modification of the graphene is achieved, but the harsh conditions limit the scope of functional groups that can be introduced. Thus, there is an obvious need for efficient yet mild methods for modification of the basal plane of graphene.Recently, Papadakis et al. reported that graphene can be efficiently photo(hydro)silylated and photohydrogenated at ambient temperature using white-light irradiation, [23] with the transfer photohydrogenation of graphene with formic acid as hydrogen donor being of particular interest from a process perspective. Subsequently, Koutoulogenis et al. also reported on the hydrogen atom abstraction from aldehyde substrates by graphite achieved through irradiation of graphite flakes with visible light. [24] In the present study, we have explored aliphatic alcohols as reaction partners to chemical vapor deposition (CVD)-grown graphene on Si/SiO 2 , kish graphite as well as highly oriented pyrolytic graphite (HOPG) under white-light irradiation, and we report on a novel mode of covalent graphene functionalization by 2-propanol (isopropyl alcohol (IPA)) that results in significantly more polar material than what is obtained from photo(hydro)silylation or photohydrogenation.Similar to formic acid, IPA is a known transfer hydrogenation reagent in metal-catalyzed reactions, [25] but reactions employing IPA resulted in a substantial increase of the polarity of "on chip" graphene after white-light irradiation. This is very different from what was obtained using formic acid [23] and a strong indication that IPA, in contrast to formic acid, is not Herein, a photochemical method for functionalization of graphene using 2-propanol is reported. The functionalization method which is catalyst-free operates at ambient temperature in neat 2-propanol under an inert atmosphere of argon. The equipment requirement is a white-light source for the irradiation. The same methodology when applied to kish graphite results in a novel material, exhibiting significantly higher wettability than the starting material according to water contact angle ...

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Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4

Cited by 44 publications

References 45 publications

Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells

Nanostructures of diamond, graphene oxide and graphite inhibit CYP1A2, CYP2D6 and CYP3A4 enzymes and downregulate their genes in liver cells

The Dispersion State of Tangled Multi-Walled Carbon Nanotubes Affects Their Cytotoxicity

White‐Light Photoassisted Covalent Functionalization of Graphene Using 2‐Propanol

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