Nanoparticles that modulate innate immunity can act as vaccine adjuvants and antigen carriers and are promising alternatives to conventional anticancer therapy. Nanoparticles might, upon contact with serum, activate the complement system that might in turn result in clearance and allergic reactions. Herein, we report that ultrasmall glyconanoparticles decorated with nonimmunogenic α-(1–6)-oligomannans trigger an innate immune response without drastically affecting the complement system. These negatively charged glyconanoparticles (10–15 nm) are stable in water and secrete proinflammatory cytokines from macrophages via the NF-κB signaling pathway. The glyconanoparticles can be used as immunomodulators for monotherapy or in combination with drugs and vaccines.
