Suppression of Sepsis Cytokine Storm by Escherichia Coli Cell Wall-Derived Carbon Dots.

Summary

E. coli cell wall–derived carbon dots (E-CDs) attenuated inflammatory cytokine production, preserved organ function, and improved survival in septic mice. Mechanistically, E-CDs competitively bound LBP–LPS, promoted lysosomal degradation of TLR4, suppressed NF-κB signaling, and reduced oxidative stress and mtDNA release to dampen the STING pathway. In septic cynomolgus monkeys and patient PBMCs, E-CDs also reduced inflammation and oxidative stress.

Key Findings

• E-CDs reduced inflammatory cytokine production, preserved organ functions, and improved survival in septic mice.
• E-CDs competitively bound to LBP with LPS, promoted lysosomal degradation of TLR4, and inhibited NF-κB activation.
• Antioxidant properties of E-CDs reduced oxidative stress and mitochondrial DNA release, suppressing STING pathway overactivation.
• E-CDs alleviated inflammation and oxidative stress in septic cynomolgus monkeys and human patient PBMCs.

Clinical Implications

While preclinical, this platform suggests a novel immunomodulatory therapy for cytokine storm in sepsis, potentially complementing antibiotics by targeting LPS–TLR4 signaling and oxidative stress pathways.

Limitations

• Preclinical evidence; no human in vivo efficacy or safety data.
• Manufacturing, scalability, biodistribution, and immunogenicity profiles of E-CDs require rigorous evaluation.

Future Directions

Define pharmacokinetics/toxicology and dose–response in large animals, optimize manufacturing under GMP, and design early-phase clinical trials in high-risk sepsis populations.