title: Peritoneal macrophages mediated delivery of chitosan/siRNA nanoparticle to the lesion site in a murine radiation-induced fibrosis model.
abstract: BACKGROUND
  Radiation-induced fibrosis (RIF) is a dose-limiting complication of cancer radiotherapy and causes serious problems, i.e. restricted tissue flexibility, pain, ulceration or necrosis. Recently, we have successfully treated RIF in a mouse model by intraperitoneal administration of chitosan/siRNA nanoparticles directed towards silencing TNF alpha in local macrophage populations, but the mechanism for the therapeutic effect at the lesion site remains unclear.
  
  
  METHODS
  Using the same murine RIF model we utilized an optical imaging technique and fluorescence microscopy to investigate the uptake of chitosan/fluorescently labeled siRNA nanoparticles by peritoneal macrophages and their subsequent migration to the inflamed tissue in the RIF model.
  
  
  RESULTS
  We observed strong accumulation of the fluorescent signal in the lesion site of the irradiated leg up to 24 hours using the optical imaging system. We further confirm by immunohistochemical staining that Cy3 labeled siRNA resides in macrophages of the irradiated leg.
  
  
  CONCLUSIONS
  We provide a proof-of-concept for host macrophage trafficking towards the inflamed region in a murine RIF model, which thereby suggests that the chitosan/siRNA nanoparticle may constitute a general treatment for inflammatory diseases using the natural homing potential of macrophages to inflammatory sites.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO) , Aarhus University, Aarhus C , Denmark.
authors.forename: Isabel
authors.initials: I
authors.lastname: Nawroth
authors.forename: Jan
authors.initials: J
authors.lastname: Alsner
authors.forename: Bent W
authors.initials: BW
authors.lastname: Deleuran
authors.forename: Frederik
authors.initials: F
authors.lastname: Dagnaes-Hansen
authors.forename: Chuanxu
authors.initials: C
authors.lastname: Yang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Horsman
authors.forename: Jens
authors.initials: J
authors.lastname: Overgaard
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Howard
authors.forename: Jørgen
authors.initials: J
authors.lastname: Kjems
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D007274:Injections, Intraperitoneal; D017737:Macrophages, Peritoneal / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics*; D017564:Radiation Pneumonitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012871:Skin Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D048271:Chitosan