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Related Concept Videos

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...

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Related Experiment Video

Updated: Jul 12, 2026

A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
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Sivelestat-Loaded Neutrophil-Membrane-Coated Antioxidative Nanoparticles for Targeted Endothelial Protection in

Juexian Wei1, Aijia Zhong2, Yuting Zhang3

  • 1Department of Emergency, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China.

Pharmaceutics
|June 27, 2025
PubMed
Summary

Neutrophil-membrane-coated nanoparticles deliver sivelestat precisely to treat sepsis-induced endothelial injury. This targeted nanotherapy reduces inflammation and protects endothelial cells, improving survival rates in sepsis models.

Keywords:
ROS scavengingdrug delivery systemendothelial injuryneutrophil-membrane-coated nanoparticlessepsissivelestat

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Pharmacology

Background:

  • Sepsis-induced endothelial injury contributes to organ failure, necessitating advanced therapeutic strategies.
  • Conventional sepsis treatments face limitations in effectively targeting damaged endothelia and mitigating dysfunction.
  • Neutrophil-membrane-coated nanoparticles offer a potential solution for site-specific drug delivery.

Purpose of the Study:

  • To develop and evaluate neutrophil-membrane-coated nanoparticles (Siv@NMs) encapsulating sivelestat for sepsis-induced endothelial injury.
  • To leverage neutrophil membrane properties for targeted delivery of sivelestat to damaged endothelia.
  • To assess the therapeutic efficacy of Siv@NMs in mitigating endothelial dysfunction and improving sepsis outcomes.

Main Methods:

  • Siv@NMs were synthesized using ultrasonication and extrusion, encapsulating sivelestat within neutrophil-membrane vesicles.
  • Physicochemical properties, stability, and drug release kinetics were characterized.
  • In vitro studies assessed biocompatibility, targeting efficiency, and ROS-scavenging capacity; in vivo efficacy was evaluated in a cecal ligation and puncture (CLP) sepsis mouse model.

Main Results:

  • Optimized Siv@NMs (approx. 150 nm, -10 mV zeta potential) showed selective binding to inflammatory endothelial cells with minimal cytotoxicity.
  • Siv@NMs significantly reduced reactive oxygen species (ROS) accumulation and attenuated endothelial injury biomarkers (ICAM-1, iNOS).
  • In vitro and in vivo studies demonstrated suppressed neutrophil extracellular trap formation and improved survival rates compared to free sivelestat.

Conclusions:

  • Neutrophil-membrane-coated nanoparticles represent a precision therapy for sepsis-associated endothelial injury.
  • The bioengineered system provides targeted drug delivery with multimodal therapeutic effects, including ROS mitigation and endothelial protection.
  • Siv@NMs show significant potential for clinical translation as a next-generation nanotherapeutic for sepsis management.