title: Dendrimer-induced leukocyte procoagulant activity depends on particle size and surface charge.
abstract: OBJECTIVE
  Thrombogenicity associated with the induction of leukocyte procoagulant activity (PCA) is a common complication in sepsis and cancer. Since nanoparticles are increasingly used for drug delivery, their interaction with coagulation systems is an important part of the safety assessment. The purpose of this study was to investigate the effects of nanoparticle physicochemical properties on leukocyte PCA, and to get insight into the mechanism of PCA induction.
  
  
  METHODS
  A total of 12 formulations of polyamidoamine (PAMAM) dendrimers, varying in size and surface charge, were studied in vitro using recalcification time assay.
  
  
  RESULTS
  Irrespective of their size, anionic and neutral dendrimers did not induce leukocyte PCA in vitro. Cationic particles induced PCA in a size- and charge-dependent manner. The mechanism of PCA induction was similar to that of doxorubicin. Cationic dendrimers were also found to exacerbate endotoxin-induced PCA.
  
  
  CONCLUSIONS
  PAMAM dendrimer-induced leukocyte PCA depends on particle size, charge and density of surface groups.
authors.affiliation: Nanotechnology Characterization Lab SAIC-Frederick Inc., NCI-Frederick 1050 Boyles St., Bldg. 469 Frederick, MD 21702, USA. marina@mail.nih.gov
authors.forename: Marina A
authors.initials: MA
authors.lastname: Dobrovolskaia
authors.forename: Anil K
authors.initials: AK
authors.lastname: Patri
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Potter
authors.forename: Jamie C
authors.initials: JC
authors.lastname: Rodriguez
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Hall
authors.forename: Scott E
authors.initials: SE
authors.lastname: McNeil
mesh_terms: D001779:Blood Coagulation Factors / Q000276:immunology*; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology*; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D055672:Static Electricity
chemical_list: D001779:Blood Coagulation Factors; D050091:Dendrimers; D053769:Nanocapsules; C104700:PAMAM Starburst; C045071:leukocyte procoagulant activity