Alphavbeta3-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 nanotherapy, 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
Hui-Fang
HF
Division of Rheumatology, Washington University School of Medicine, St. Louis, Missouri, USA.
Chan
Happy W
HW
Wickline
Samuel A
SA
Lanza
Gregory M
GM
Pham
Christine T N
CT
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D003510:Cyclohexanes / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D039302:Integrin alphaVbeta3 / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D039302:Integrin alphaVbeta3; D012717:Sesquiterpenes; C026211:fumagillin