title: Selective Localization of a Novel Dendrimer Nanoparticle in Myocardial Ischemia-Reperfusion Injury.
abstract: BACKGROUND
  Dendrimer nanoparticle therapies represent promising new approaches to drug delivery, particularly in diseases associated with inflammatory injury. However, their application has not been fully explored in models of acute myocardial ischemia (MI) and reperfusion injury.
  
  
  METHODS
  White male New Zealand rabbits underwent left thoracotomy with 30-minute temporary left anterior descending artery occlusion and MI confirmed by electrocardiography and histology (MI rabbits, n = 9), or left thoracotomy and pericardial opening for 30 minutes but no left anterior descending artery occlusion (control [C] rabbits, n = 9) rabbits. Following the 30-minute period, a dendrimer (generation 6 dendrimer conjugated to cyanine-5 fluorescent dye [G6-Cy5], 6.7 nm diameter) was administered intravenously and the chest closed in layers. Animals were sacrificed at 3 hours (3 MI, 3 C), 24 hours (3 MI, 3 C), or 48 hours (3 MI, 3 C) postsurgery.
  
  
  RESULTS
  As compared to controls, MI rabbits had twofold G6-Cy5 uptake in the myocardial anterior wall as compared to the same region in nonischemic control rabbits at 24 hours postsurgery (6.01 ± 0.57 μg/g versus 2.85 ± 0.85 μg/g; p = 0.04). This trend was also present at 48 hours (6.38 ± 1.53 μg/g versus 3.95 ± 0.60 μg/g, p = 0.21) and was qualitatively evident on confocal microscopy. G6-Cy5 half-life in serum was approximately 12 hours, with 22% of the injected G6-Cy5 dose remaining at 48 hours.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that dendrimer nanodevices selectively localize in ischemic as compared to healthy myocardium. This indicates that dendrimer nanodevices are promising agents to deliver drugs specifically to the ischemic myocardium to attenuate the injury. Subsequent studies will assess the efficacy of a dendrimer-drug conjugate in ameliorating reperfusion injury following MI.
authors.affiliation: Division of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: J Trent
authors.initials: JT
authors.lastname: Magruder
authors.affiliation: Division of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Crawford
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Lin
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Division of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Grimm
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Rangaramanujam M
authors.initials: RM
authors.lastname: Kannan
authors.affiliation: Center for Nanomedicine, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Sujatha
authors.initials: S
authors.lastname: Kannan
authors.affiliation: Division of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: csciort2@jhmi.edu.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sciortino
mesh_terms: D000818:Animals; D050091:Dendrimers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004562:Electrocardiography; D008297:Male; D018613:Microscopy, Confocal; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D053758:Nanoparticles; D011817:Rabbits
chemical_list: D050091:Dendrimers