title: Lung toxicity and biodistribution of Cd/Se-ZnS quantum dots with different surface functional groups after pulmonary exposure in rats.
abstract: BACKGROUND
  The potential use of quantum dots (QD) in biomedical applications, as well as in other systems that take advantage of their unique physiochemical properties, has led to concern regarding their toxicity, potential systemic distribution, and biopersistence. In addition, little is known about workplace exposure to QD in research, manufacturing, or medical settings. The goal of the present study was to assess pulmonary toxicity, clearance, and biodistribution of QD with different functional groups in rats after pulmonary exposure.
  
  
  METHODS
  QD were composed of a cadmium-selenide (CdSe) core (~5nm) with a zinc sulfide (ZnS) shell functionalized with carboxyl (QD-COOH) or amine (QD-NH2) terminal groups. Male Sprague-Dawley rats were intratracheally-instilled (IT) with saline, QD-COOH, or QD-NH2 (12.5, 5.0, or 1.25 μg/rat). On days 0, 1, 3, 5, 7, 14, and 28 post-IT, the left lung, lung-associated lymph nodes (LALN), heart, kidneys, spleen, liver, brain, and blood were collected for metal analysis of Cd content by neutron activation to evaluate clearance and biodistribution. One right lobe was ligated and fixed for microscopy and histopathological analysis. The remaining right lobes from rats in each group were subjected to bronchoalveolar lavage (BAL) to retrieve BAL fluid and cells for analysis of injury and inflammation.
  
  
  RESULTS
  Lung injury and inflammation was found to be dose-dependent and peaked at days 7 and 14 post-exposure for both forms of QD, with slight variations in degree of toxicity at early and later time points. Both QD appeared to lose their fluorescent properties and destabilize after 1 week in the lung. Cd persisted up to 28 days for both forms of QD; however, clearance rate was slightly greater for QD-COOH over time. No Cd was detected in the liver, spleen, heart, brain, or blood at any time point. Cd appeared in the LALN and kidneys beginning at 1-2 weeks post-exposure.
  
  
  CONCLUSIONS
  QD-COOH and QD-NH2 differed in clearance rate and differed slightly in degree of toxicity at different time points; however, the overall pattern of toxicity and biodistribution was similar between the two particles. Toxicity may be dependent on the dissolution rate and bioavailability of free Cd.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jur6@cdc.gov
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Chapman
authors.forename: James F
authors.initials: JF
authors.lastname: Scabilloni
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Robert R
authors.initials: RR
authors.lastname: Mercer
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019187:Cadmium Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D055370:Lung Injury / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045663:Quantum Dots; D051381:Rats; D017207:Rats, Sprague-Dawley; D018036:Selenium Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D013440:Sulfides / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D013499:Surface Properties; D014018:Tissue Distribution; D017967:Zinc Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D019187:Cadmium Compounds; D018036:Selenium Compounds; D013440:Sulfides; D017967:Zinc Compounds; C058667:cadmium selenide; C031238:zinc sulfide