title: Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the inhibitory effects of the nanoparticle-mediated delivery of plasminogen kringle 5 (K5) on choroidal neovascularization (CNV) and retinal inflammation.
  
  
  METHODS
  CNV was induced by laser in adult rats. Nanoparticles with an expression plasmid of K5 (K5-NP) were injected into the vitreous. K5 expression was detected by immunohistochemistry. The CNV area was measured after fluorescein angiography. Retinal vascular permeability was quantified with Evans blue as a tracer. Expression of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 was measured by Western blot analysis or ELISA and real-time RT-PCR.
  
  
  RESULTS
  Intense K5 expression was detected in the retina 2 weeks after the injection of K5-NP. Areas of CNV were significantly decreased in the K5-NP treatment group compared with that in the control-NP group. The K5-NP injection also significantly reduced vascular permeability. The expression of VEGF was downregulated by K5-NP at both the protein and mRNA levels. Moreover, K5-NP also inhibited expression of TNF-α and ICAM-1. Similarly, K5-NP decreased retinal levels of total β-catenin. In cultured cells, K5-NP suppressed hypoxia-induced secretion of MCP-1 and TNF-α.
  
  
  CONCLUSIONS
  K5 has a novel anti-inflammatory activity. K5-NP mediates a sustained inhibitory effect on CNV and thus has therapeutic potential for age-related macular degeneration.
authors.affiliation: Department of Ophthalmology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Jin
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Zhou
authors.forename: Kyoungmin
authors.initials: K
authors.lastname: Park
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zheng
authors.forename: Puneet
authors.initials: P
authors.lastname: Tyagi
authors.forename: Uday B
authors.initials: UB
authors.lastname: Kompella
authors.forename: Jian-xing
authors.initials: JX
authors.lastname: Ma
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015153:Blotting, Western; D002199:Capillary Permeability; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D048271:Chitosan; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D058449:Intravitreal Injections; D019344:Lactic Acid; D008297:Male; D053758:Nanoparticles; D010446:Peptide Fragments / Q000008:administration & dosage*; D010958:Plasminogen / Q000008:administration & dosage*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C491499:plasminogen kringle 5; C467498:vascular endothelial growth factor A, rat; D018799:Intercellular Adhesion Molecule-1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010958:Plasminogen; D048271:Chitosan