Polyhydroxylated nanoparticle surfaces activate complement. (a) Synthesis and stabilization with two different forms of Pluronic allowed the generation of polyhydroxylated- or polymethoxylated-nanoparticles. (b) The, -terminal OH groups on Pluronic could be converted to OCH3 groups. (c) The proposed mechanism where OH groups on the polyhydroxylated nanoparticles can bind to the exposed thioester of C3b to activate complement by the alternative pathway. (d) Nanoparticle-induced complement activation, as measured through C3a presence in human serum after incubation with nanoparticles, was demonstrated to be high with polyhydroxylated nanoparticles but low with polymethoxylated nanoparticles (OH- and CH3O-NPs, respectively). Results are normalized to control of serum incubation with PBS. Values are means of three independent experiments; error bars correspond to standard error of mean, s.e.m. Reproduced with permission.[200] Copyright 2007, Nature Publishing Group.