Functionalized core-shell nanogel scavenger for immune modulation therapy in sepsis

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Sepsis is a life-threatening condition characterized by hyperinflammation, organ failure, and high mortality.
• Current treatment options for sepsis are limited, highlighting the need for novel therapeutic strategies.
• Hyperinflammation in sepsis involves the overproduction of pro-inflammatory cytokines and the presence of endotoxins like lipopolysaccharides (LPS).

Purpose of the Study:

• To develop and evaluate a core-shell hydrogel nanoparticle functionalized with telodendrimer (TD) nanotrap (NT) for controlling sepsis-induced hyperinflammation.
• To investigate the nanoparticle's ability to selectively scavenge inflammatory molecules and cytokines.
• To assess the therapeutic efficacy of the TD NT nanogel in preclinical models of sepsis.

Main Methods:

• Synthesis of a core-shell hydrogel nanoparticle with a TD-functionalized core and a crosslinked shell.
• Characterization of the nanoparticle's size-selective scavenging properties for molecules like LPS and cytokines.
• In vitro and in vivo evaluation of the TD NT nanogel's efficacy in reducing inflammation markers (e.g., cytokine production, NF-κB activation) in LPS-induced sepsis models.

Main Results:

• The TD NT nanogel demonstrated size-selective scavenging, excluding large proteins while capturing medium-sized molecules (10-30 kDa) like LPS.
• The nanogel effectively captured pro-inflammatory cytokines both in vitro and in vivo.
• Intraperitoneal administration of the TD NT nanogel significantly attenuated NF-κB activation and cytokine production in septic mouse models.

Conclusions:

• The core-shell TD NT nanogel is a promising therapeutic agent for controlling hyperinflammation in sepsis.
• The nanoparticle's ability to selectively remove inflammatory mediators offers a novel approach to sepsis treatment.
• Injectable TD NT core-shell nanogels have potential applications in attenuating both local and systemic inflammation.