Activation of the Complement System: Morphological Differences in the Surface of PIBCA Nanoparticles Coated with Polysaccharides

Drug-loaded nanosystems are often associated with the advantages of controlled drug release and reduced toxicity. Understanding the activation of the complement system by polysaccharide-coated nanosystems becomes a crucial step in the development of new nanomedicines since the nonactivation of the complement system allows the nanosystems to circulate blood for longer. The aim of this study was to evaluate the activation of the complement system via the C3 protein pathway by polyisobutylcyanoacrylate (PIBCA) nanoparticles coated with polysaccharides (fucoidan, chitosan, or levan) with different surface morphologies. To this end, the nanoparticles were developed using anionic emulsion polymerization (AEP) and redox emulsion polymerization (RREP) techniques were applied to obtain nanoparticles with the same chemical composition but different polysaccharide architectures. The complement system activation studies were carried out using the 2D immunoelectrophoresis technique. Polysaccharide-coated nanoparticles were obtained with sizes ranging from 99.0 ± 0.5 to 659.9 ± 39.0 nm. As expected, the surface charge of the nanoparticles varied as a function of the polysaccharide coating: positive charges for chitosan-NPs, negative charges for fucoidan-NPs, and neutral charges for levan-NPs. According to the results, Chi-NPs did not activate the complement system, while Fuc-NPs and Lev-NPs did, depending on the surface morphology of the polysaccharides. The nanoparticles (Fuc-NPs and Lev-NPs) obtained by the AEP technique were strong complement activators, and those obtained by the RREP technique seemed to induce the formation of aggregates with the C3b protein. The molecular docking results reinforce these findings, highlighting the regions of the polysaccharide interaction with the C3 and C3b proteins. The presence of some chemical groups, such as the sulfate groups present in fucoidan, on the surface of the nanoparticles may contribute to the activation of the complement system.