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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    • "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.
    Journal of Biomedical Nanotechnology 09/2015; 11(9). DOI:10.1166/jbn.2015.2093 · 5.34 Impact Factor
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    • "For the PPE SCKs, immunotoxicity was also higher for cationic SCKs (12 cytokines) than for anionic SCKs (3 cytokines), whereas the zwitterionic SCKs did not induce the secretions of any of the tested cytokines. These proinflammatory cytokines have been well studied and characterized as participants in the basic inflammatory process and mediators of cellular infiltration525354555657. Degradation products of PPE-micelles and SCKs induced minimal release of the tested cytokines. "
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    ABSTRACT: The construction of nanostructures from biodegradable precursors and shell/core crosslinking have been pursued as strategies to solve the problems of toxicity and limited stability, respectively. Polyphosphoester (PPE)-based micelles and crosslinked nanoparticles with non-ionic, anionic, cationic, and zwitterionic surface characteristics for potential packaging and delivery of therapeutic and diagnostic agents, were constructed using a quick and efficient synthetic strategy, and importantly, demonstrated remarkable differences in terms of cytotoxicity, immunotoxicity, and biofouling properties, as a function of their surface characteristics and also with dependence on crosslinking throughout the shell layers. For instance, crosslinking of zwitterionic micelles significantly reduced the immunotoxicity, as evidenced from the absence of secretions of any of the 23 measured cytokines from RAW 264.7 mouse macrophages treated with the nanoparticles. The micelles and their crosslinked analogs demonstrated lower cytotoxicity than several commercially-available vehicles, and their degradation products were not cytotoxic to cells at the range of the tested concentrations. PPE-nanoparticles are expected to have broad implications in clinical nanomedicine as alternative vehicles to those involved in several of the currently available medications.
    Scientific Reports 11/2013; 3:3313. DOI:10.1038/srep03313 · 5.58 Impact Factor
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    • "The uptake of QDs into the liver, spleen, lung, kidneys and bone marrow varies on the basis of their surface moieties (Fischer et al., 2006). The incorporation of polyethylene glycol (PEG) as QD surface coating reduces their nonspecific binding to several types of cells (Zhang et al., 2008). When attached to the surface of QDs, PEG of different molecular weights produces differential tissue and organ deposition in mice in a time-and size-dependent manner (Ballou et al., 2004). "
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    ABSTRACT: Quantum dots (QDs) are novel tools with multiple biological and medical applications because of their superior photoemission and photostability characteristics. However, leaching of toxic metals from QDs is of great concern. Therefore, for the successful application of QDs in bioscience, it is essential to understand their biological fate and toxicity. We investigated toxicological effects and tissue distribution of mercaptopropionic acid-conjugated cadmium selenide/cadmium sulfide (CdSe/CdS-MPA) QDs after repeated intraperitoneal injection into BALB/c mice. The mice were injected every 3 days with various doses of QDs (0, 5, 10 and 25 mg kg(-1) ). The subsequent effects of QDs on plasma levels of various biomarkers were evaluated at different time points (at 0, 1, 4, 7, 10, 13 and 15 days). Various tissue samples (spleen, liver, lung, kidneys, brain, heart and thymus) were collected for toxicity analysis, distribution testing, histopathological examination and inflammation assessment. No abnormal clinical signs or behaviors were recorded but the body weight of mice treated with 25 mg kg(-1) QDs was significantly decreased from day 7 compared with control mice. QDs were observed in the liver, spleen, lung and kidneys, but not in brain or heart. Significantly higher levels of lactate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase were found in the plasma, liver and spleen. Histopathological examination did not show any tissue toxicity but the levels of interleukin-6, a pro-inflammatory marker, were increased in the plasma, liver and spleen. All of these findings provide insight into the observed toxicological effect levels and tissue-specific distribution of CdSe/CdS-MPA QDs. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 09/2013; 33(9). DOI:10.1002/jat.2775 · 2.98 Impact Factor
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