title: Polyethyleneimine-functionalized iron oxide nanoparticles for systemic siRNA delivery in experimental arthritis.
abstract: OBJECTIVE
  This study aimed to examine the efficacy of a nanocarrier (polyethyleneimine [PEI]-superparamagnetic iron oxide nanoparticle [SPIO]), composed of a core of iron oxide and a shell of PEI, in the systemic delivery of therapeutic siRNA to experimental arthritic joints.
  
  
  METHODS
  PEI-SPIO/siRNA nanoparticles were synthesized and characterized in vitro. Nanoparticles were administered intravenously to arthritic rats to analyze cellular uptake, tissue distribution and the therapeutic effect of a siRNA against the IL-2/-15 receptor β chain (IL-2/IL-15Rβ).
  
  
  RESULTS
  PEI-SPIOs loaded with siRNA displayed negligible cytotoxicity, improved siRNA stability, efficient uptake by macrophages and the ability to induce specific gene silencing in vitro. PEI-SPIO-delivered siRNA accumulated easily in inflamed joints and was efficiently taken up by joint macrophages and T cells. Although IL-2/IL-15Rβ siRNA-loaded PEI-SPIOs alone were efficacious in the treatment of experimental arthritis, combination therapy with both PEI-SPIO/IL-2/IL-15Rβ siRNA and a magnetic field displayed an additive anti-inflammatory effect.
  
  
  CONCLUSIONS
  PEI-functionalized SPIOs can be employed for systemic siRNA delivery in rheumatoid arthritis and enhanced therapeutic benefit can be achieved by the use of an external magnetic field.
authors.affiliation: Key Laboratory of Ministry of Education for Developmental Genes & Human Diseases, School of Life Sciences, Southeast University, Nanjing, China.
authors.forename: Juanli
authors.initials: J
authors.lastname: Duan
authors.forename: Jinlai
authors.initials: J
authors.lastname: Dong
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhang
authors.forename: Zhenyi
authors.initials: Z
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Mao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000628:therapy; D002417:Cattle; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D007376:Interleukin-2 / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D011094:Polyethyleneimine / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D058185:Magnetite Nanoparticles; D034741:RNA, Small Interfering; C000499:ferric oxide; D011094:Polyethyleneimine
keywords: IL-2/IL-15Rb; macrophage; nanoparticle; rheumatoid arthritis; siRNA