title: Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes.
abstract: 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.
authors.affiliation: Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
authors.forename: Leshuai W
authors.initials: LW
authors.lastname: Zhang
authors.forename: William W
authors.initials: WW
authors.lastname: Yu
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Colvin
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Monteiro-Riviere
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005453:Fluorescence; D005470:Fluorometry / Q000379:methods; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007378:Interleukins / Q000378:metabolism; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D045663:Quantum Dots; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D036121:Receptor, EphA3; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; C491718:EPHA3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3