title: Low Concentrations of Cationic PAMAM Dendrimers Affect Lymphocyte Respiration in In vitro Studies.
abstract: BACKGROUND
  In this study, the effect of low concentrations of poly(amido)amine dendrimers (G2-G4) on human lymphocytes was studied. Some works revealed that PAMAMs can adversely affect the morphology of blood components and mitochondria functions. In this context, the present report aimed to investigate the in vitro cationic dendrimers' effect on mitochondrial respiration and cell morphology in lymphocytes isolated from human blood.
  
  
  METHODS
  To monitor the mitochondrial changes, the high-resolution respirometer was used, whereas the cell morphology was analyzed using a flow cytometer and fluorescence microscopy.
  
  
  RESULTS
  The concentration-dependent dendrimers' influence on lymphocytes morphology was shown. Changes in mitochondrial respiration revealed the concentration- and generation-dependent differences between dendrimer activity. There were no alterations in the routine respiration and in the state of the inner mitochondrial membrane (L/E), but decreased ADP- and FCCP-stimulated respirations were detected after treatment with G3 and G4 dendrimers. The markers of mitochondrial membrane integrity (RCR) and OXPHOS efficiency (P/E) significantly decreased regardless of the dendrimer generation used.
  
  
  CONCLUSIONS
  Based on these in vitro evaluations, we state that cationic PAMAM dendrimers can impair both the morphology and the bioenergetics of human lymphocytes, even when used at low concentrations and in a short time (up to 1 h). However, these results do not imply that similar findings could be possible for in vivo observations.
authors.affiliation: Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz. Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Labieniec-Watala
authors.forename: Marzena
authors.initials: M
authors.lastname: Szwed
authors.forename: Joanna
authors.initials: J
authors.lastname: Hertel
authors.forename: Ewelina
authors.initials: E
authors.lastname: Wisnik
mesh_terms: D002412:Cations; D019069:Cell Respiration / Q000187:drug effects*; D002478:Cells, Cultured; D050091:Dendrimers / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*
chemical_list: D002412:Cations; D050091:Dendrimers; C104700:PAMAM Starburst; D010100:Oxygen
keywords: Biomaterials; PAMAM dendrimers; mitochondria; morphology; nanotechnology; toxicity