Enzyme Inhibition and Bioapplications

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Some issues related to toxicity and biosafety became pertinent during preliminary biological application of GO [ 41 ]. Graphene materials consist of solely carbon. However, it is a matter of serious concern to understand how carbon derivatives like GO and RGO behave in a biological system and how long it takes to excrete from the human body [ 9 ]. However, during fabrication, GBNs usually undergo several chemical treatment processes for functionalization, including doping with metals, oxidation, which introduces functional groups, and also a material reduction.

It is known from the information on structural properties of GBNs that graphene is a hydrophobic material, so it requires modification of functional groups to make it a biomedical material. This modification may include covalent and non-covalent functionalization. Non-covalent functionalization improves dispersibility, biocompatibility, reactivity, binding capacity or sensing [ 28 ].

The formation of hydrogen bonds between polar functional groups on the GO surface and water molecules forms a stable GO colloidal suspension for potential biomedical applications of GO [ 43 , 44 ].

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In bioapplications, both oxidized GO and reduced RGO graphene oxides are found to be feasible for drug delivery and therapeutic applications. The principal advantage of using GO over other carbon-based materials is due to its aqueous and colloidal stability. The physicochemical characteristics of GO that make it a chemically versatile template with a high surface-to-volume ratio facilitate a variety of biomedical applications such as imaging and cancer therapy, and biosensing.

Apart from GO, graphene and RGO have been found to be promising photosensitizing agents for photo-ablation because they generate heat upon irradiation, making it possible for application in combined theranostic therapies. It was expected that in , there will be 1, , new cancer cases diagnosed and , cancer deaths in the USA [ 55 , 56 ].

Compared to the normal tissues, tumor tissues usually possess unique microstructural features, unique microenvironment and physicochemical properties such as abnormal temperature gradients, weak acidity, overexpressed proteins and enzymes [ 57 , 58 , 59 , 60 ]. The altered tumor intracellular environments, such as pH inside of endosomes and lysosomes, are considered when developing the anticancer drug that releases upon reaching the targeted site. For the past two decades, the rapid development in nanotechnology for the diagnosis and treatment of cancer has greatly improved.

Among the carbon nanomaterials, GBNs gained popularity in anticancer research. Several studies have contributed to the delivery of GBN-based chemotherapeutics for the treatment of cancer. All great potential of graphene oxide cancer therapies encouraged many researchers to combine multifunctionalities for cancer treatment. In this section, we have summarized the recent reports on the various anticancer drugs used as therapeutics along with GBNs.

Competitive and Noncompetitive Enzymatic Inhibition - Michaelis-Menten Kinetics

The versatility of GBNs and various studies confirm that GBNs could be used as antimicrobial agents [ 98 , 99 , , , , , , , , , , , ]. GBNs and their nanocomposites were used as antibacterial in many fields such as in controlling microbial pathogens [ ], wound dressing [ , ], tissue engineering [ , , ], packaging [ ], drug delivery [ ] and the purification of water [ ]. The promising applications of GBNs as antibacterial in various fields listed are drug delivery, surface infection, dental fillers, membrane antibiotic fouling, water disinfection and food packaging [ ].

There are also a vast number of studies on the antibacterial activity of GO and RGO with other metal and metal oxides. In addition, the synergistic antibacterial activity of GBNs was evaluated along with other metal and metal oxides. For example, GO sheets were hybridized with silver nanoparticles AgNPs via one-pot hydrothermal, electrostatics interactions, simple missing chemical deposition, sequential repetitive chemical reductions and supercritical CO 2. Recently, the contradictory reports on the antibacterial activity of functionalized GBNs have been discussed by Hegab et al. Increasing number of investigations on the antibacterial activity of GBNs postulated several important mechanisms of antibacterial activity [ , ].

Recently, GBNs have been widely reported to have antibacterial activity with their sharp edges to bacterial membranes leading to the destruction of lipid biomolecules and oxidative stress [ ]. Zhao et al. Therefore, it is necessary to compare different types of GBNs and their effects on the bacterial species to their physiochemical characteristics.

GBNs physiochemical parameters, impurities from the synthesis process, a method of antibacterial testing and experimental conditions should be considered for the GBNs which are explored for biomedical applications.


Bioimaging is an important aspect of diagnostic research, as it can be used to monitor the health conditions of biological components in typically two types of environments, in vivo and in vitro. The primary requirements of materials used for bioimaging are high specificity, non-toxicity and sensitivity. While graphene can alleviate the toxicity of fabricated probes, introducing the selectivity and sensitivity is still a challenge in the material synthesis.

The initial studies on GQDs as imaging probes were reported in the early s, wherein GQDs were prepared by hydrothermal cutting of graphene sheets [ 21 ]. As these dots showed remarkable photo-physical properties, fluorescence spectroscopy was the commonly used technique for imaging biological components. The numbers in the parentheses are respective references. The cell death caused by nanomaterials includes either necrosis triggered by reactive oxygen species or apoptosis via plasma membrane damage.

In the past few years, many reviews had published on the toxicity of GBNs in cells and animal models. The review by Ou et al. Moreover, Syama et al. Only minimal or unnoticeable GO toxicity in the lungs and other organs [ ] Graphene [0. Male Sprague—Dawley rats No dose-dependent effects and no distinct lung pathology were observed.

The two aspects that demonstrate the behavior of GBNs in biological fluids are the behavior of graphene as a colloid and the formation of the graphene surface of the protein corona. The GBNs in colloid form interact with the physiological media resulting in aggregation and flocculation of the suspension.

Another critical factor affecting the behavior of GBNs is the formation of a protein corona. They explain that two components soft and hard corona play a significant role in adsorbing proteins. The particle stability may be enhanced if proteins are adsorbed via hydrophobic region to the basal plane of the flake with the hydrophilic region directed toward the exterior. On the other hand, adverse reactions may occur with the biodistribution and the interaction with the immune system. Hence, it is confirmed that the systemic adverse reactions are caused by GBNs or by modifications performed to GBNs [ ].

Cells exposed to nanomaterial may undergo both apoptosis and necrosis. Chemical and physical properties such as reactive oxygen species ROS and direct damage to plasma membrane may trigger apoptosis and necrosis respectively. Many reports were published on the internalization of GBNs as therapeutic agents as well as they might lead to cell intoxication [ ]. The complication of intravenous drug delivery of GBNs bioaccumulation and granuloma formation can be overcome by surface modifications to accomplish selective targeting and support biodegradation [ ].

Graphene is emerging as a dynamic nanocarbon material. Although there are a broad scope and numerous advantages of GBNs in different fields of the scientific world, they also cause toxic effects on different biological models. An increase in the production of GBNs and their expected usage for biomedical purposes raises anxiety about their effects on humans and environment. It is necessary to understand the interaction of GBNs with the living systems to advance the biomedical application of GBNs.

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Even though the health effects associated with the GBNs have been studied at the cellular and in animal model, the human exposure of GBNs is unknown. Humans can be affected by GBNs via various exposure routes Fig. Thereby, both the abiotic and biotic compartments of the ecosystem will get disturbed. It is imperative to investigate the interaction of GBNs across the membranes in the ecosystem to estimate the risk potential of the GBNs released into the environment. Very few reports found the impact of GBNs on the environment.

Choudhury et al. They reported that exposure to sunlight has a significant impact on the physiochemical properties of GO and their subsequent transport by reducing the materials stability in the environment. The research needs to be conducted to understand the complex roles of pH, natural organic material and other natural colloids on the fate of photo-transformed GO. Hua et al. The findings indicated that the graphene oxide nanoparticles GONPs transport and fate has a significant impact in natural aquatic environments by divalent cations, natural organic matter NOM and hydraulics [ ].

Dreyer, R. Ruoff, C.

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1. Introduction

Cha, S. Shin, N. Annabi, M. Dokmeci, A. Khademhosseini, Carbon-based nanomaterials: multifunctional materials for biomedical engineering. ACS Nano 7 4 , — Compton, S.

Nguyen, Graphene oxide, highly reduced graphene oxide, and graphene: versatile building blocks for carbon-based materials. Small 6 6 , — Wang, Carbon-nanotube based electrochemical biosensors: a review. Electroanalysis 17 1 , 7—14 Dresselhaus, P. Avouris, Introduction to carbon materials research. Tonelli, V. Goulart, K. Gomes, M. Ladeira, A. Santos, E. Ladeira, R.

Resende, Graphene-based nanomaterials: biological and medical applications and toxicity. Nanomedicine 10 15 , — Yoo, J. Kang, B. Hong, Graphene-based nanomaterials for versatile imaging studies. Zhu, S.

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Enzyme Inhibition and Bioapplications Enzyme Inhibition and Bioapplications
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