Functionalized Core–Shell Nanogel Scavenger for Immune Modulation Therapy in Sepsis

Sepsis is a complex, life-threatening hyperinflammatory syndrome associated with organ failure and high mortality due to lack of effective treatment options. Here, a core–shell hydrogel nanoparticle with the core functionalized with telodendrimer (TD) nanotrap (NT) to control hyperinflammation in sepsis is reported. The combination of multivalent charged and hydrophobic moieties in TD enables effective binding with biomolecules in NT. The higher crosslinking in the shell structure of nanogel excludes the abundant large serum proteins and allows for size-selectivity in scavenging the medium-sized septic molecules (10–30 kDa), e.g., lipopolysaccharides (LPS, a potent endotoxin in sepsis), thus reducing cytokine production. At the same time, the core–shell TD NT nanogel captures the overflowing proinflammatory cytokines effectively both in vitro and in vivo from biological fluids to further control hyperinflammation. Intraperitoneal injection of core–shell TD NT nanogel effectively attenuates NF-κB activation and cytokine production in LPS-induced septic mouse models. These results indicate the potential applications of the injectable TD NT core–shell nanogel to attenuate local or systemic inflammation.