Anti-inflammatory and antiangiogenic effects of nanoparticle-mediated delivery of a natural angiogenic inhibitor.

Abstract

PURPOSE:

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: Ji Jin, Kevin K Zhou, Kyoungmin Park, Yang Hu, Xun Xu, Zhi Zheng, Puneet Tyagi, Uday B Kompella, Jian-xing Ma
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 52 Issue 9 Pg. 6230-7 (Aug 05 2011) ISSN: 1552-5783 [Electronic] United States
• PMID: 21357401 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Angiogenesis Inhibitors
• Anti-Inflammatory Agents
• Ccl2 protein, rat
• Chemokine CCL2
• Peptide Fragments
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Vascular Endothelial Growth Factor A
• plasminogen kringle 5
• vascular endothelial growth factor A, rat
• Intercellular Adhesion Molecule-1
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Plasminogen
• Chitosan

Topics

• Angiogenesis Inhibitors (administration & dosage)
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Blotting, Western
• Capillary Permeability
• Chemokine CCL2 (genetics, metabolism)
• Chitosan
• Choroidal Neovascularization (drug therapy, genetics, metabolism)
• Drug Delivery Systems
• Enzyme-Linked Immunosorbent Assay
• Fluorescein Angiography
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Intravitreal Injections
• Lactic Acid
• Male
• Nanoparticles
• Peptide Fragments (administration & dosage)
• Plasminogen (administration & dosage)
• Polyglycolic Acid
• Polylactic Acid-Polyglycolic Acid Copolymer
• RNA, Messenger (metabolism)
• Rats
• Rats, Inbred BN
• Reverse Transcriptase Polymerase Chain Reaction
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)