In Vitro Three‐Dimensional Liver Models for Nanomaterial DNA Damage Assessment

Llewellyn, S.; Niemeijer, Marije; Nymark, Penny; Moné, Martijn J.; Water, Bob van de; Conway, Gillian E; Jenkins, Glyn; Doak, Shareen H.

doi:10.1002/smll.202006055

Cited by 19 publications

(21 citation statements)

References 118 publications

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“…One of the major drawbacks of the primary cell culture-based models is the fast dedifferentiation and deviation of the hepatic phenotype over time which makes them unsuitable for long-term exposure studies. [122,123] On the other hand, immortalized cell lines such as HepG2 exhibit reduced metabolic activity, specifically cytochrome P450 (CYP450) enzymes. [123][124][125] A reliable in vitro model needs to be remained phenotypically stable and retain morphology, viability, and hepatocyte-specific functions for culture prolonged periods (weeks).…”

Section: Metabolism: Liver Modelsmentioning

confidence: 99%

“…[122,123] On the other hand, immortalized cell lines such as HepG2 exhibit reduced metabolic activity, specifically cytochrome P450 (CYP450) enzymes. [123][124][125] A reliable in vitro model needs to be remained phenotypically stable and retain morphology, viability, and hepatocyte-specific functions for culture prolonged periods (weeks). Table 3 lists some of the reported MPS-based models of the liver with their anatomical structure, functions and achieved results.…”

Section: Metabolism: Liver Modelsmentioning

confidence: 99%

“…Several excellent reviews recently published discuss liver-on-a-chip systems with more details. [123,126,127] Bavli et al [128] developed a liver on-chip device that enables real-time monitoring of metabolic function and maintaining the tissue under physiological conditions for one month. Realtime monitoring of mitochondrial respiration was enabled using two-frequency phase modulation of tissue-embedded phosphorescent microprobes.…”

Section: Metabolism: Liver Modelsmentioning

confidence: 99%

“…Several excellent reviews recently published discuss liver‐on‐a‐chip systems with more details. [ 123,126,127 ]…”

Section: Progress Of Chip‐based Absorption Studies (Permeability and Bioavailability)mentioning

confidence: 99%

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Pharmacokinetics‐On‐a‐Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

et al. 2021

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pharmacodynamics (PD), and toxicity studies, of the past century and continue to provide a wealth of knowledge and understanding of various diseases mechanism and therapy. [1][2][3] However, the use of these models in research and industrial applications has been a subject of heated debate, particularly, due to ethical matters and the increasing pressure by the animalright activists. [4] In addition, the phylogenetic difference between laboratory animals and humans may lead to drug failure during human clinical studies. [5] Furthermore, the inherent complexity of the animal's body tissue makes it difficult to interpret the physiological events that characterize the interaction of a particular organ or cells with exogenic factors. [6] In line with regulatory developments precluding the use of animal testing, human in vitro methodologies is required to replace the animal-based testes while permitting equivalent or superior prediction. [7,8] Despite many efforts, no sufficiently acceptable in vitro approaches have been developed to date, and the major gap to predict drug response in human still existed. Utilizing animal models can lead to significant insights into the complex pathophysiology of the disease. [9] However, the pathophysiology may differ between humans and animals. [10,11] Comparing to animal model-based studies, these interactions are less well understood in humans. This is a necessity considering the differences between animal and human immune responses and outcomes in preclinical models versus clinical trials. [10,11] There is consequently a real need for in vitro models of the human organs that closely mimic the physiological processes of disease development with an acceptable level of flexibility, accuracy, and reproducibility for efficient screening of potential drug candidates. Such models would increase the predictability of human response to drugs and reduce experimentation expenses and speed up the screening processes. Failing to produce safe and efficient preclinical leads and drug candidates is associated with overall low R&D efficiency and high cost. The cost of developing a new drug that gains marketing approval is estimated to be $2.6 billion (as of 2013) which includes the in vitro and in vivo animal models during the preclinical and clinical trials stages which may last several Despite many ongoing efforts across the full spectrum of pharmaceutical and biotech industries, drug development is still a costly undertaking that involves a high risk of failure during clinical trials. Animal models played vital roles in understanding the mechanism of human diseases. However, the use of these models has been a subject of heated debate, particularly due to ethical matters and the inevitable pathophysiological differences between animals and humans. Current in vitro models lack the sufficient functionality and predictivity of human pharmacokinetics and toxicity, therefore, are not capable to fully replace animal models. The recent development of microphysiological systems has shown great potentia...

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Section: Metabolism: Liver Modelsmentioning

confidence: 99%

Section: Metabolism: Liver Modelsmentioning

confidence: 99%

Section: Metabolism: Liver Modelsmentioning

confidence: 99%

“…Several excellent reviews recently published discuss liver‐on‐a‐chip systems with more details. [ 123,126,127 ]…”

Section: Progress Of Chip‐based Absorption Studies (Permeability and Bioavailability)mentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetics‐On‐a‐Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

et al. 2021

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“…[2][3][4] Several types of researches have been considered to study the interactions between nanomaterials and biomolecules such as proteins, RNA and DNA. [5,6] As a matter of fact, noncovalent interactions determine the structure of biomacromolecules. Among them, hydrogen bonding and electrostatic interactions have been expected to have a principal role.…”

Section: Introductionmentioning

confidence: 99%

Effect of COF Presence on DNA Molecular Interactions: A QM/MM and MD Simulations Study

Ghadari

Mohsenzadeh

2021

ChemistrySelect

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Four models of DNA including A-DNA, B-DNA, Triple helix-DNA (T-DNA), and Z-DNA along with a COF molecule were prepared. Molecular dynamics simulations were performed on all DNAs and their complex with COF (embedded DNAs in the central hole of COF). Comprehensive analyses such as Base pair distance, hydrogen bonding, Van der Waals, and electrostatic interaction numbers were carried out to investigate the effect of COF molecule on DNA intermolecular interactions. Furthermore, quantum-mechanics studies were performed to explore the accuracy of intermolecular and intramolecular interactions. The results obtained based on promolecular density in two selected base pairs. Noncovalent interaction (NCI) analysis to investigate the strength of hydrogen bonds, Van der Waals interactions, and steric effect was done. Density Overlap Regions Indicator (DORI) analysis was accomplished to study the accuracy of π-π stacking interactions between adjacent bases. δg functions were evaluated to analyze the strength of chemical bonds, hydrogen bonds and also the steric effect. The average distance between O … H, N … H, and H … O that are contributing in H-bonding are ∼ 1.88, 1.97, and 1.95 Å in A-DNA, respectively. Also, the average number of H-bonding numbers in A-DNA calculated to be 14.43 and 13.04 in pure and complex form. All the achieved results showed that designed COF did not make any changes in DNA structures, but in some cases, had some effects on the interactions of DNAs.

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Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications

Chen

Xia

2022

Advanced Materials

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vaccines, and drug carriers (Figure 1). The functional advantages of NMs are derived from their unique physical and chemical properties. [1,[4][5][6] Among all the NMs, metallic NMs including metal and metal oxides (MOx) nanoparticles (NPs), such as Ag and Au NPs, transition-metal oxides (TMOs, e.g., SiO 2 , Co 3 O 4 , and Mn 2 O 3 ), and rare-earth oxides REOs (e.g., Gd 2 O 3 , La 2 O 3 , and Y 2 O 3 ) NPs, are among the most produced NMs worldwide. Also, they are widely used in consumer products such as dietary supplements, fuel additives, cosmetics, bioimaging, and drug carriers, etc. due to their properties such as small size, high surface area, controlled particle shape as well as superior mechanical, electronic, optical, and magnetic properties. [7][8][9] For example, SiO 2 NPs have been applied in the theranostic fields, including bioimaging and targeted drug delivery. [7] In addition, the popularity of carbon nanomaterials (CNMs) including 0D fullerenes, 1D carbon nanotubes (CNTs), and 2D graphene-based nanoparticles (GBN) including graphene, graphene oxide (GO), and reduced graphene oxide (rGO) has been on the rise for their applications in battery, electronics, drug delivery, bio-sensing, bio-imaging, and tissue engineering due to their large surface area, diverse surface functional groups, excellent optical property, and efficient drug-loading capacity. [10][11][12][13][14][15][16] For example, an advanced NMsbased biosensing platform based on rGO has been developed to detect the coronavirus disease 2019 (COVID-19) antibodies within seconds. [17] Additionally, a form of nanostructured cellulose (nanocellulose), including cellulose nanocrystal (CNC) and cellulose nanofiber (CNF) has been increasingly considered for applications in papermaking, coatings, food, nanocomposite formulations and reinforcement, and biomedical fields (e.g., wound dressing) due to its biocompatibility, outstanding mechanical, chemical, and rheological properties. [18,19] Also 2D transition metal dichalcogenides (TMDs) (including MoS 2 and BN) with high surface area and free surface energy levels are increasingly being used for commercial applications in energy generation, sensors, catalysis, electronics, and biomedicine fields. [13,[20][21][22] Similarly, organic NPs (including lipid, liposome, polymer, micelle, dendrimer, and protein/peptide-based NPs) have been widely used in diagnosis, drug delivery, bioimaging, and cancer therapy because of their facile synthesis and chemical modification, self-assembly, biocompatibility, and biodegradability. [23][24][25] The global market value of NMs will be expected to reach US$ 125 billion marks by 2024. [26] The widespread Nanomaterials (NMs) are widely used in commercial and medical products, such as cosmetics, vaccines, and drug carriers. Exposure to NMs via various routes such as dermal, inhalation, and ingestion has been shown to gain access to the systemic circulation, resulting in the accumulation of NMs in the liver. The unique organ structures and blood flow features facilitate...

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In Vitro Three‐Dimensional Liver Models for Nanomaterial DNA Damage Assessment

Cited by 19 publications

References 118 publications

Pharmacokinetics‐On‐a‐Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

Pharmacokinetics‐On‐a‐Chip: In Vitro Microphysiological Models for Emulating of Drugs ADME

Effect of COF Presence on DNA Molecular Interactions: A QM/MM and MD Simulations Study

Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications

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