Fate and Toxicity of Metallic and Metal‐Containing Nanoparticles for Biomedical Applications

Li, Yu Feng; Chen, Chunying

doi:10.1002/smll.201101059

Cited by 214 publications

(128 citation statements)

References 151 publications

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“…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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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 their small size, nanoparticles may cross biological barriers to reach a number of organs, and according to their size and surface properties, accumulation of metal nanoparticles has been observed previously in all organs in vivo. 19 Generation of free oxygen radicals and oxidative stress triggers a host of cellular events, including DNA damage and apoptosis. 20 Therefore, in the present study, an attempt was made to assess the toxicity and apoptotic potential of TiO 2 nanoparticles in the liver tissue of male rats.…”

Section: Introductionmentioning

confidence: 99%

Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats

Alarifi¹,

Ali²,

Al‐Doaiss³

et al. 2013

IJN

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Titanium dioxide (TiO 2 ) nanoparticles are among the top five nanoparticles used in consumer products, paints, and pharmaceutical preparations. Given that exposure to such nanoparticles is mainly via the skin and inhalation, the present study was conducted in male Wistar albino rats (Rattus norvegicus). Our aim was to investigate the effect of TiO 2 nanoparticles on hepatic tissue in an attempt to understand their toxicity and the potential effect of their therapeutic and diagnostic use. To investigate the effects of TiO 2 nanoparticles on liver tissue, 30 healthy male Wistar albino rats were exposed to TiO 2 nanoparticles at doses of 63 mg, 126 mg, and 252 mg per animal for 24 and 48 hours. Serum glutamate oxaloacetate transaminase and alkaline phosphatase activity was altered. Changes in hepatocytes can be summarized as hydropic degeneration, cloudy swelling, fatty degeneration, portal and lobular infiltration by chronic inflammatory cells, and congested dilated central veins. The histologic alterations observed might be an indication of hepatocyte injury due to the toxicity of TiO 2 nanoparticles, resulting in an inability to deal with accumulated residues from the metabolic and structural disturbances caused by these nanoparticles. The appearance of cytoplasmic degeneration and destruction of nuclei in hepatocytes suggests that TiO 2 nanoparticles interact with proteins and enzymes in hepatic tissue, interfering with antioxidant defense mechanisms and leading to generation of reactive oxygen species which, in turn, may induce stress in hepatocytes, promoting atrophy, apoptosis, and necrosis. More immunohistochemical and ultrastructural investigations are needed in relation to TiO 2 nanoparticles and their potential effects when used as therapeutic and diagnostic tools.

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“…[31][32][33] For example, a polyethylene glycol coating on a gold NP with a hydrodynamic size of 27.6 nm in size at doses ranging from 0.17-4.26 mg/kg results in acute inflammation and apoptosis of hepatocytes following intravenous administration compared to no abnormalities or acute toxicities following intravenous administration of 2 mg/kg of gum arabic-coated gold NPs with a hydrodynamic size of 85 nm. 31,33 In mouse model studies using gold nanoparticles, the median lethal dose is 3.2 g of Au per kg. 34 Since dogs in our study were administered much lower doses of gold -a maximum of 0.325 mg of gold -no tissue toxicity from gold alone was anticipated.…”

Section: Discussionmentioning

confidence: 99%

Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

Axiak‐Bechtel¹,

Upendran²,

Lattimer³

et al. 2014

IJN

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Introduction Gum arabic-coated radioactive gold nanoparticles (GA- 198 AuNPs) offer several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA- 198 AuNPs injected intralesionally. We proposed that a single treatment of GA- 198 AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity. Methods Nine dogs with spontaneously occurring prostatic cancer were treated. Injections were performed with ultrasound or computerized tomography guidance. Complete blood counts, chemistry panels, and urinalyses were performed at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection. Planar scintigraphic images were obtained within 30 minutes of injection. Results No statistically significant difference was found in any hematologic or biochemical parameter studied, nor was any evidence of tumor swelling or abscessation found in eight dogs with repeat imaging; one dog died secondary to urethral obstruction 12 days following injection. At 30 minutes postinjection, an average of 53% of injected dose in seven dogs was retained in the prostate, with loss of remaining activity in the bladder and urethra; no systemic uptake was detected. Conclusion GA- 198 AuNP therapy had no short-term toxicity in the treatment of prostatic cancer. While therapeutic agent was found in the prostate immediately following injection, some loss of agent was detected in the bladder and urethra. Localization of radioactivity within the prostate was lower than anticipated and likely due to normal vestigial prostatic ducts. Therefore, further study of retention, dosimetry, long-term toxicity, and efficacy of this treatment is warranted prior to Phase I trials in men.

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Fate and Toxicity of Metallic and Metal‐Containing Nanoparticles for Biomedical Applications

Cited by 214 publications

References 151 publications

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

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

Histologic and apoptotic changes induced by titanium dioxide nanoparticles in the livers of rats

Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

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