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Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum

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A novel nanodrug formulation targets intestinal injury in sepsis. This approach neutralizes inflammatory cytokines and inhibits cell death, significantly improving survival rates in septic mice.

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broad‐spectrum anti‐inflammationolaparibpH‐responsive capsulesparthanatossepsis‐induced intestinal injury

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Immunology

Background:

  • Sepsis is a life-threatening condition with high mortality rates.
  • The intestine is a critical organ in sepsis progression, and its barrier function is often compromised.
  • Current sepsis therapies offer limited protection for the intestinal barrier.

Purpose of the Study:

  • To develop an advanced nanodrug formulation for targeted intestinal delivery in sepsis.
  • To investigate the therapeutic efficacy of this formulation in a mouse model of sepsis.

Main Methods:

  • Formulation of intestine-decipher engineered capsules (cp-OLA@MΦ NPs) containing olaparib-loaded, macrophage membrane-coated nanoparticles (OLA@MΦ NPs).
  • Oral administration of cp-OLA@MΦ NPs in septic mice.
  • Evaluation of nanoparticle targeting, cytokine neutralization, inhibition of parthanatos, bacterial translocation, and survival rates.

Main Results:

  • The engineered capsules successfully delivered nanodrugs to injured intestinal tissues in septic mice.
  • The nanodrugs effectively neutralized pro-inflammatory cytokines and inhibited poly(ADP-ribose) polymerase 1 (PARP1)-mediated cell death.
  • Treatment significantly reduced bacterial translocation and improved survival rates in septic mice.

Conclusions:

  • The developed nanodrug delivery system shows promise for treating sepsis by protecting the intestinal barrier and modulating the immune response.
  • This strategy offers a potential new therapeutic avenue for clinical sepsis management.