Biological Interactions of Quantum Dot Nanoparticles in Skin and in Human Epidermal Keratinocytes

Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.71). 04/2008; 228(2):200-11. DOI: 10.1016/j.taap.2007.12.022
Source: PubMed


Quantum dots nanoparticles have novel optical properties for biomedical applications and electronics, but little is known about their skin permeability and interaction with cells. QD621 are nail-shaped nanoparticles that contain a cadmium/selenide core with a cadmium sulfide shell coated with polyethylene glycol (PEG) and are soluble in water. QD were topically applied to porcine skin flow-through diffusion cells to assess penetration at 1 microM, 2 microM and 10 microM for 24 h. QD were also studied in human epidermal keratinocytes (HEK) to determine cellular uptake, cytotoxicity and inflammatory potential. Confocal microscopy depicted the penetration of QD621 through the uppermost stratum corneum (SC) layers of the epidermis and fluorescence was found primarily in the SC and near hair follicles. QD were found in the intercellular lipid bilayers of the SC by transmission electron microscopy (TEM). Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD both did not detect Cd nor fluorescence signal in the perfusate at any time point or concentration. In HEK, viability decreased significantly (p<0.05) from 1.25 nM to 10 nM after 24 h and 48 h. There was a significant increase in IL-6 at 1.25 nM to 10 nM, while IL-8 increased from 2.5 nM to 10 nM after 24 h and 48 h. TEM of HEK treated with 10 nM of QD621 at 24 h depicted QD in cytoplasmic vacuoles and at the periphery of the cell membranes. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, yet if the skin were damaged allowing direct QD exposure to skin or keratinocytes, an inflammatory response could be initiated.

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Available from: Nancy A Monteiro-Riviere, Apr 30, 2015
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    • "In terms of dermal exposures, QDs can be taken by human keratinocyte cells and showed little toxicity up to 20 nM in concentration (Zhang et al., 2011). QDs have also been shown to penetrate into the outer layers of stratum corneum and epidermis, but not all the way through, porcine skin (Zhang et al., 2008). In contrast, pulmonary exposure to QDs (a potential route of exposure in occupational settings) has been shown to result in neutrophilic and granulomatous inflammation, compromised alveolar-capillary barrier function, DNA damage, and cytotoxicity (Oberdorster et al., 2005; Jacobsen et al., 2009; Ma-Hock et al., 2012, 2013; Ho et al., 2013; Roberts et al., 2013). "
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    ABSTRACT: Quantum dots (QDs) are engineered semiconductor nanoparticles with unique physicochemical properties that make them potentially useful in clinical, research and industrial settings. However, a growing body of evidence indicates that like other engineered nanomaterials, QDs have the potential to be respiratory hazards, especially in the context of the manufacture of QDs and products containing them, as well as exposures to consumers using these products. The overall goal of this study was to investigate the role of mouse strain in determining susceptibility to QD-induced pulmonary inflammation and toxicity. Male mice from 8 genetically diverse inbred strains (the Collaborative Cross founder strains) were exposed to CdSe-ZnS core-shell QDs stabilized with an amphiphilic polymer. QD treatment resulted in significant increases in the percentage of neutrophils and levels of cytokines present in bronchoalveolar lavage fluid (BALF) obtained from NOD/ShiLtJ and NZO/HlLtJ mice relative to their saline (Sal) treated controls. Cadmium measurements in lung tissue indicated strain-dependent differences in disposition of QDs in the lung. Total glutathione levels in lung tissue were significantly correlated with percent neutrophils in BALF as well as with lung tissue Cd levels. Our findings indicate that QD-induced acute lung inflammation is mouse strain dependent, that it is heritable, and that the choice of mouse strain is an important consideration in planning QD toxicity studies. These data also suggest that formal genetic analyses using additional strains or recombinant inbred strains from these mice could be useful for discovering potential QD-induced inflammation susceptibility loci.
    Full-text · Article · Oct 2015 · Toxicology and Applied Pharmacology
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    • "Since systemic localization and retention has been established for most routes of entry, research has moved towards actively understanding the impact of skin barrier disruption and interaction with cell types most likely to incidentally encounter these nanoparticles . Research by our group and others has investigated the ability of QDs to penetrate the skin, an organ likely to encounter QDs, and found that under most conditions an intact skin barrier is adequate protec- tion [10] [11] [12] [13] . However, barrier impairment by such methods as UVB exposure [10] [14] , tape stripping [15] , dermal abrasion [12] [13] , and low frequency sonophoresis [16] can increase risk of QD exposure to the body system and the local cell types. "
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    ABSTRACT: Studies have shown that UVB can slightly increase the penetration of nanoparticles through skin and significantly alter skin cell biology, thus it is important to understand if and how UVB may impact subsequent nanoparticle skin cell interactions. The research presented herein evaluates the effect of UVB on quantum dot (QD) uptake and reactive oxygen species (ROS) generation in primary keratinocytes, primary melanocytes, and related cell lines. QD exposure induced cell type dependent ROS responses increased by pre-exposing cells to UVB and correlated with the level of QD uptake. Our results suggest that keratinocytes may be at greater risk for QD induced ROS generation than melanocytes, and raise awareness about the differential cellular effects that topically applied nanomaterials may have on UVB exposed skin.
    Full-text · Article · Sep 2015 · Journal of Biomedical Nanotechnology
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    • "When used in biomedical applications, these materials will likely be introduced into patients however disposal of consumer products containing QDs may also result in their release into the environment at high local concentrations, where they might accumulate and degrade (Kahru and Ivask, 2013; Scheringer, 2008). Our current knowledge of the potential health effects of exposure to QDs is mainly derived from acute cytotoxicity studies, and the data generated suggest that QDs may exert adverse effects in the skin (Zhang et al., 2008), lungs (Geys et al., 2008; Jacobsen et al., 2009), gastrointestinal tract (Wang et al., 2008), and other tissues (Soenen et al., 2012; Tang et al., 2008). The debate surrounding the potential toxicity of QDs still persists ; for instance, no toxicity could be found in a pilot study on non-human primates (Ye et al., 2012). "
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