Aggregation and Protein Corona Formation on Gold Nanoparticles Affect Viability and Liver Functions of Primary Rat Hepatocytes

Koh, Wee Ling; Tham, Phoebe Huijun; Yu, Hanry; Leo, Hwa Liang; Kah, James Chen Yong

doi:10.2217/nnm-2016-0173

Cited by 18 publications

(9 citation statements)

References 52 publications

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“…All GO samples showed hydrodynamic diameter sizes of 320–460 nm in RPMI 1640 medium compared to a size range of 550–600 nm in BEGM medium; the reduced size in the former medium is due to the presence of a high concentration of serum albumin, which leads to the formation of a protein corona. 19, 20…”

Section: Resultsmentioning

confidence: 99%

“…Most GO samples showed agglomeration in DI H 2 O, resulting in hydrodynamic diameters of 330–440 nm, except for rGO-2 that showed larger (550 nm) agglomerates as a result of reduced hydrophilicity. All GO samples showed hydrodynamic diameter sizes of 320–460 nm in RPMI 1640 medium compared to a size range of 550–600 nm in BEGM medium; the reduced size in the former medium is due to the presence of a high concentration of serum albumin, which leads to the formation of a protein corona. , …”

Section: Resultsmentioning

confidence: 99%

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Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model

et al. 2018

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While two-dimensional graphene oxide (GO) is used increasingly in biomedical applications, there is uncertainty on how specific physicochemical properties relate to biocompatibility in mammalian systems. Although properties such as lateral size and the colloidal properties of the nanosheets are important, the specific material properties that we address here is the oxidation state and reactive surface groups on the planar surface. In this study, we used a GO library, comprising pristine, reduced (rGO), and hydrated GO (hGO), in which quantitative assessment of the hydroxyl, carboxyl, epoxy, and carbon radical contents was used to study the impact on epithelial cells and macrophages, as well as in the murine lung. Strikingly, we observed that hGO, which exhibits the highest carbon radical density, was responsible for the generation of cell death in THP-1 and BEAS-2B cells as a consequence of lipid peroxidation of the surface membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser effects, while rGO showed extensive cellular uptake with minimal effects on viability. In order to see how these in vitro effects relate to adverse outcomes in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal sacrifice after 40 h demonstrated that hGO was more prone than other materials to generate acute lung inflammation, accompanied by the highest lipid peroxidation in alveolar macrophages, cytokine production (LIX, MCP-1), and LDH release in bronchoalveolar lavage fluid. Pristine GO showed less toxicity, whereas rGO had minimal effects. We demonstrate that the surface oxidation state and carbon radical content play major roles in the induction of toxicity by GO in mammalian cells and the lung.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model

et al. 2018

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“…Thus, an acute burst of exposure to GNPs is more harmful to cells, and cells can adapt to protect themselves against long-term nanoparticle exposure. Another in-vitro study on primary rat hepatocytes showed that both citrate and protein corona coated GNPs exerted only an acute effect on the albumin synthesis of hepatocytes, with no chronic impact [ 29 ]. Thus, the acute phase toxicity of GNPs after the first dose followed by the recovery phase, even after the subsequent exposure of GNPs, is in agreement with previous reports that have shown the absence of toxicity in animals that were treated with multiple doses of GNPs [ 16 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Histopathology of the Liver, Kidney, and Spleen of Mice Exposed to Gold Nanoparticles

et al. 2018

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Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections with a gap of one week) of 5 nm, 20 nm, and 50 nm diameter GNPs on the structural and biochemical changes in the liver, kidney, and spleen of mice. The results showed that small sized GNPs (5 nm) produced significant pathological changes in the liver on day 2 that gradually reduced on day 8. The medium (20 nm) and large (50 nm) sized GNPs preferentially targeted the spleen and caused significant pathological changes to the spleen architecture on day 2 that persisted on day 8 as well. There were minimal and insignificant pathological changes to the kidneys irrespective of the GNPs size. The animals that were primed with the pre-exposure of GNPs did not show any aggravation of histological changes after the second dose of the same GNPs. None of the dose regimens of the GNPs were able to significantly affect the markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) in all of the organs that were studied. In conclusion, the size of GNPs plays an important role in their pathological effects on different organs of mice. Moreover, the primed animals become refractory to further pathological changes after the second dose of GNPs, suggesting the importance of a priming dose in medical applications of GNPs.

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“…PC-coated NPs strongly differ in size, surface charge and aggregation state compared to pristine NPs. 6–8 PC composition is affected by both NP characteristics (e.g., physicochemical properties) and environmental factors (e.g., temperature, protein source, type of disease present). The effect of NPs’ physicochemical properties on corona formation have been extensively examined and already comprehensively reviewed by us and others.…”

Section: Introductionmentioning

confidence: 99%

Personalized protein corona on nanoparticles and its clinical implications

et al. 2017

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It is now well understood that once in contact with biological fluids, nanoscale objects lose their original identity and acquire a new biological character, referred to as a protein corona. The protein corona changes many of the physicochemical properties of nanoparticles, including size, surface charge, and aggregation state. These changes, in turn, affect the biological fate of nanoparticles, including their pharmacokinetics, biodistribution, and therapeutic efficacy. It is progressively being accepted that even slight variations in the composition of a protein source (e.g., plasma and serum) can substantially change the composition of the corona formed on the surface of the exact same nanoparticles. Recently it has been shown that the protein corona is strongly affected by the patient’s specific disease. Therefore, the same nanomaterial incubated with plasma proteins of patients with different pathologies adsorb protein coronas with different compositions, giving rise to the concept of personalized protein corona. Herein, we review this concept along with recent advances on the topic, with a particular focus on clinical relevance.

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Aggregation and Protein Corona Formation on Gold Nanoparticles Affect Viability and Liver Functions of Primary Rat Hepatocytes

Abstract: The AuNP-Cor showed higher cell uptake and reduced cell viability compared with aggregated AuNP-Cit. Urea and albumin secretions showed AuNP dose dependency. Both AuNP-Cit and AuNP-Cor exerted only an acute effect on the albumin synthesis of hepatocytes with no chronic impact.

Cited by 18 publications

References 52 publications

Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model

Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model

Histopathology of the Liver, Kidney, and Spleen of Mice Exposed to Gold Nanoparticles

Personalized protein corona on nanoparticles and its clinical implications

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