Surface coatings determine cytotoxicity and irritation potential of quantum dot nanoparticles in epidermal keratinocytes.

Quantum dot (QD) nanoparticles have potential applications in nanomedicine as drug delivery vectors and diagnostic agents, but the skin toxicity and irritation potential of QDs are unknown. Human epidermal keratinocytes (HEKs) were used to assess if QDs with different surface coatings would cause differential effects on HEK cytotoxicity, proinflammatory cytokine release, and cellular uptake. Commercially available QDs of two different sizes, QD 565 and QD 655, with neutral (polyethylene glycol (PEG)), cationic (PEG-amine), or anionic (carboxylic acid) coatings were utilized. Live cell imaging and transmission electron microscopy were used to determine that all QDs localized intracellularly by 24 hours, with evidence of QD localization in the nucleus. Cytotoxicity and release of the proinflammatory cytokines IL-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha were assessed at 24 and 48 hours. Cytotoxicity was observed for QD 565 and QD 655 coated with carboxylic acids or PEG-amine by 48 hours, with little cytotoxicity observed for PEG-coated QDs. Only carboxylic acid-coated QDs significantly increased release of IL-1beta, IL-6, and IL-8. These data indicate that QD surface coating is a primary determinant of cytotoxicity and immunotoxicity in HEKs, which is consistent across size. However, uptake of QDs by HEKs is independent of surface coating.

[1]  N. Monteiro-Riviere,et al.  Analysis of interleukin-8 release from normal human epidermal keratinocytes exposed to aliphatic hydrocarbons: delivery of hydrocarbons to cell cultures via complexation with alpha-cyclodextrin. , 2001, Toxicology in vitro : an international journal published in association with BIBRA.

[2]  M. Nirmal,et al.  Fluorescence intermittency in single cadmium selenide nanocrystals , 1996, Nature.

[3]  Nancy A. Monteiro-Riviere,et al.  Challenges for assessing carbon nanomaterial toxicity to the skin , 2006 .

[4]  Hassan S. Bazzi,et al.  Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots , 2005, Journal of Molecular Medicine.

[5]  N. Monteiro-Riviere,et al.  Identification of early biomarkers of inflammation produced by keratinocytes exposed to jet fuels jet A, JP‐8, and JP‐8(100) , 2000, Journal of biochemical and molecular toxicology.

[6]  Ron C. Hardman.  A Toxicologic Review of Quantum Dots: Toxicity Depends on Physicochemical and Environmental Factors , 2005, Environmental health perspectives.

[7]  S. Ullrich,et al.  Dermal application of JP-8 jet fuel induces immune suppression. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[8]  N. Monteiro-Riviere,et al.  Pyridostigmine bromide modulates topical irritant-induced cytokine release from human epidermal keratinocytes and isolated perfused porcine skin. , 2003, Toxicology.

[9]  B. Nickoloff,et al.  The cytokine network in psoriasis. , 1991, Archives of dermatology.

[10]  G. Oberdörster,et al.  Pulmonary effects of inhaled ultrafine particles , 2000, International archives of occupational and environmental health.

[11]  Amane Shiohara,et al.  On the Cyto‐Toxicity Caused by Quantum Dots , 2004, Microbiology and immunology.

[12]  V. Dixit,et al.  Keratinocytes as initiators of inflammation , 1991, The Lancet.

[13]  R. Nemanich,et al.  Multi-walled carbon nanotube interactions with human epidermal keratinocytes. , 2005, Toxicology letters.

[14]  R. Nemanich,et al.  Surfactant effects on carbon nanotube interactions with human keratinocytes. , 2005, Nanomedicine : nanotechnology, biology, and medicine.

[15]  N. Monteiro-Riviere,et al.  The cytotoxicity of jet fuel aromatic hydrocarbons and dose-related interleukin-8 release from human epidermal keratinocytes , 2003, Archives of Toxicology.

[16]  Mark Green,et al.  Semiconductor quantum dots and free radical induced DNA nicking. , 2005, Chemical communications.

[17]  N. Monteiro-Riviere,et al.  Penetration of intact skin by quantum dots with diverse physicochemical properties. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[18]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[19]  Sung Ju Cho,et al.  Unmodified cadmium telluride quantum dots induce reactive oxygen species formation leading to multiple organelle damage and cell death. , 2005, Chemistry & biology.

[20]  J. Matthew Mauro,et al.  Long-term multiple color imaging of live cells using quantum dot bioconjugates , 2003, Nature Biotechnology.

[21]  Karluss Thomas,et al.  Research strategies for safety evaluation of nanomaterials, part V: role of dissolution in biological fate and effects of nanoscale particles. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[22]  S. Bhatia,et al.  Probing the Cytotoxicity Of Semiconductor Quantum Dots. , 2004, Nano letters.

[23]  N. Monteiro-Riviere,et al.  Differential relationship between the carbon chain length of jet fuel aliphatic hydrocarbons and their ability to induce cytotoxicity vs. interleukin-8 release in human epidermal keratinocytes. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  Toxicology of Nanomaterials , 2006 .

[25]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[26]  Samir Mitragotri,et al.  Low-frequency sonophoresis: ultrastructural basis for stratum corneum permeability assessed using quantum dots. , 2006, The Journal of investigative dermatology.