Fumagillin prodrug nanoparticles (Fum-PD NP) suppress KRN arthritis and inflammatory response. Mice were injected ip with 150 μL of KRN serum on day 0. Changes in ankle thickness (A) and arthritis score (B) were assessed daily. Starting on day 2, when early arthritis was clearly established, mice were randomly divided into groups and given serial daily injections of targeted NPs without drug (Ctrl NP) or Fum-PD NPs for three consecutive doses. On day 9 the animals were sacrificed; their paws were harvested and homogenized, and paw lysates analyzed for inflammatory cytokine levels (C–F). (G) Day 9 paw sections were stained with Mac-3 (macrophage marker), and the number was enumerated per high power field (HPF). Values represent mean ± SEM, n = 5 mice per treatment group. *p < 0.05, **p < 0.01, ***p < 0.001. (H) Paws were also sectioned and stained for endothelial marker CD31 (PECAM-1, red) and iNOS (green). Co-localization (yellow) is indicated with arrowheads. Note tendon autofluorescence (green, arrow). Scale bar = 50 μm.