Cellular Uptake, Intracellular Trafficking, and Cytotoxicity of Nanomaterials

Zhao, Feng; Zhao, Ying; Liu, Ying; Chang, Xueling; Chen, Chunying; Zhao, Ye

doi:10.1002/smll.201100001

Cited by 1,001 publications

(808 citation statements)

References 144 publications

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“…50 Nanoparticles degradable in macrophages may be cleared by the RES organs, while nondegradable particles may be deposited in organs for a long time. 52,53 Other excretion pathways, including loss in saliva, sweat, and breast milk, are also possible. 54 Using lower organisms like Caenorhabditis elegans as study models, the ADME of nanoparticles are also found.…”

Section: Absorption Distribution Metabolism and Excretion Of Nanopmentioning

confidence: 99%

Perturbation of physiological systems by nanoparticles

et al. 2014

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Nanotechnology is having a tremendous impact on our society. However, societal concerns about human safety under nanoparticle exposure may derail the broad application of this promising technology. Nanoparticles may enter the human body via various routes, including respiratory pathways, the digestive tract, skin contact, intravenous injection, and implantation. After absorption, nanoparticles are carried to distal organs by the bloodstream and the lymphatic system. During this process, they interact with biological molecules and perturb physiological systems. Although some ingested or absorbed nanoparticles are eliminated, others remain in the body for a long time. The human body is composed of multiple systems that work together to maintain physiological homeostasis. The unexpected invasion of these systems by nanoparticles disturbs normal cell signaling, impairs cell and organ functions, and may even cause pathological disorders. This review examines the comprehensive health risks of exposure to nanoparticles by discussing how nanoparticles perturb various physiological systems as revealed by animal studies. The potential toxicity of nanoparticles to each physiological system and the implications of disrupting the balance among systems are emphasized.

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Section: Absorption Distribution Metabolism and Excretion Of Nanopmentioning

confidence: 99%

Perturbation of physiological systems by nanoparticles

et al. 2014

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“…This is the first study addressing the cytotoxicity of released n-CuPc fragment in macrophages. Macrophages, as a part of the cell-mediated immune system, exhibit phagocytic activity, during which the cell can phagocytose pathogens or particles, forming vesicles resulting in either biodegradation (Zhang et al, 2015;Zhao et al, 2011), antigen presentation or physical clearance via cell migration. These cells may therefore be exposed to potentially relatively high doses of particles.…”

Section: Introductionmentioning

confidence: 99%

Releases from transparent blue automobile coatings containing nanoscale copper phthalocyanine and their effects on J774 A1 macrophages

et al. 2017

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A B S T R A C TNanoscale copper phthalocyanine (n-CuPc) is a pigment widely used in paints to enhance automobile coatings and to make colors transparent and more appealing to users. Despite the benefits, n-CuPc can potentially be released into the environment and pose risks in occupational settings. Assessing the toxicity of released n-CuPccontaining fragments is thus important for the acceptance of n-CuPc products. This paper presents the first combined study addressing both the release of n-CuPc-containing fragments from commercial coatings in realistic occupational situations and the hazard of the released fragments using a macrophage model.Sanding was used to produce fragments from automobile coatings with n-CuPc as well as from a reference coating with the same matrix composition but without n-CuPc. Size distribution and agglomeration of these fragments in Rosewell Park Memorial Institute (RPMI) cell culture medium was studied before conducting a battery of cytotoxicity experiments. Cell viability and reactive oxygen species (ROS) production were conducted and particle localization within cells was analyzed.The results show similar size and number distribution of fragments when comparing the reference and n-CuPc fragments. The n-CuPc fragments showed higher agglomeration in RPMI than pristine n-CuPc. We found that toxicity of the n-CuPc fragments and reference materials was similar (EC 50 Frag n-CuPc = 242.9 μg ml − 1 ; EC 50Frag Refer = 241.6 μg ml − 1 ) and below the toxicity of pristine n-CuPc (EC 50 n-CuPc = 151.1 μg ml). The results demonstrated that embedding n-CuPc in matrix used in automobile coatings reduced the toxicity and release when n-CuPc is used in paints. Our finding can be used to support design of n-CuPc-enabled products used in automobile applications.

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“…Due to their small size, large surface area and high reactivity, the particle-induced production of ROS and oxidative injury has become an established paradigm for NP toxicity. 26,27 Another paradigm of NP toxicity is the release of toxic ions when the thermodynamic properties of a material (including surface-free energy) favor particle dissolution in a suspending medium or biological environment. 27,28 Therefore, it is important to quantify the dissolution of metal residues from CNTs into biological fluids to estimate the role of dissolved metal ions contributing to cellular toxicity.…”

Section: Introductionmentioning

confidence: 99%

The contributions of metal impurities and tube structure to the toxicity of carbon nanotube materials

et al. 2012

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Due to the existence of considerable quantities of metallic and carbonaceous impurities, the key factor and mechanism for the reported toxicity of carbon nanotubes (CNTs) are unclear. Here, we first quantify the contribution of metal residues and fiber structure to the toxicity of CNTs. Significant quantities of metal particles could be mobilized from CNTs into surrounding fluids, depending on the properties and constituents of the biological microenvironment, as well as the properties of metal particles. Furthermore, electron spin resonance measurements confirm that hydroxyl radicals can be generated by both CNTs containing metal impurities and acid-leachable metals from CNTs. Several biomolecules facilitate the generation of free radicals, which might be due to the participation of these biomolecules in redox cycling influenced by pH. Among several major metal residues, Fe has a critical role in generating hydroxyl radicals, reducing cell viability and promoting intracellular reactive oxidative species. Cell viability is highly dependent on the amount of metal residues and iron in particular, but not tube structure, while the negative effect of CNTs themselves on cell viability is very limited in a certain concentration range below 80 lg ml À1 . It is crucial to systematically understand how these exogenous and endogenous factors influence the toxicity of CNTs to avoid their undesirable toxicity. Keywords: biological microenvironments; carbon nanotube; metal impurities; reactive oxygen species; toxicity INTRODUCTION Engineered nanomaterials possess novel properties and have been used worldwide in numerous consumer products, for example, food, clothes, pharmaceuticals and cleaning products. Estimates suggest that by 2015 nanotechnology will have a trillion-plus dollar global economic impact. 1 Therefore, ensuring the safety of nanomaterials is of great importance to the tremendous commercial applications of nanotechnology. Safety evaluation of nanomaterials should consider their behaviors in various aspects, including their interaction with proteins, DNA, lipids, membranes, organelles, cells, tissues, biological fluids and even the dissolution of metal constituents. [2][3][4] Carbon nanotubes (CNTs) have attracted great interest from both scientists and the industry because their high aspect ratios, strength and remarkable physical properties make them a unique material with a wide range of promising applications. Many applications of CNTs in biomedicine have been proposed, including nanoelectronics, 4 biosensors, 5 biomolecular recognition devices and molecular transporters, 6 artificial water channels, 7 cancer therapy 8,9 and photoacoustic molecular imaging. 10 Because transitional metals are often used as catalysts during CNT synthesis, 11 it is unavoidable that as-received CNTs are contaminated by catalyst residues. 12 The catalyst precursor (such as iron carbonyl) decomposes, and nanometer-sized metal particles form from the decomposition products. Therefore,

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Cellular Uptake, Intracellular Trafficking, and Cytotoxicity of Nanomaterials

Cited by 1,001 publications

References 144 publications

Perturbation of physiological systems by nanoparticles

Perturbation of physiological systems by nanoparticles

Releases from transparent blue automobile coatings containing nanoscale copper phthalocyanine and their effects on J774 A1 macrophages

The contributions of metal impurities and tube structure to the toxicity of carbon nanotube materials

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