alpha(v)beta(3)-Targeted nanotherapy suppresses inflammatory arthritis in mice

The purpose of this study was to assess whether an alternative treatment approach that targets angiogenesis, delivered through ligand-targeted nano-therapy, would ameliorate inflammatory arthritis. Arthritis was induced using the K/BxN mouse model of inflammatory arthritis. After arthritis was clearly established, mice received three consecutive daily doses of alpha(v)beta 3-targeted fumagillin nanoparticles. Control groups received no treatment or alpha(v)beta(3)-targeted nanoparticles without drugs. Disease score and paw thickness were measured daily. Mice that received alpha(v)beta(3)-targeted fumagillin nanoparticles showed a significantly lower disease activity score (mean score of 1.4 +/- 0.4; P<0.001) and change in ankle thickness (mean increase of 0.17 +/- 0.05 mm; P<0.001) 7 d after arthritis induction, whereas the group that received alpha(v)beta(3)-targeted nanoparticles without drugs exhibited a mean arthritic score of 9.0 +/- 0.3 and mean change in ankle thickness of 1.01 +/- 0.09 mm. Meanwhile, the group that received no treatment showed a mean arthritic score of 9.8 +/- 0.5 and mean change in ankle thickness of 1.05 +/- 0.10 mm. Synovial tissues from animals treated with targeted fumagillin nanoparticles also showed significant decrease in inflammation and angiogenesis and preserved proteoglycan integrity. Ligand-targeted nanotherapy to deliver antiangiogenic agents may represent an effective way to treat inflammatory arthritis.-Zhou, H.-F., Chan, H. W., Wickline, S. A., Lanza, G. M., Pham, C. T. N. alpha(v)beta(3)-Targeted nanotherapy suppresses inflammatory arthritis in mice. FASEB J. 23, 2978-2985 (2009). www.fasebj.org