Cell membrane-formed nanovesicles for disease-targeted delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Vascular inflammation underlies many diseases.
• Current nanoparticle drug delivery methods face challenges in targeting efficacy.
• Intercellular adhesion molecule 1 (ICAM-1) is upregulated on inflamed endothelium, binding to neutrophil integrin β2.

Purpose of the Study:

• To develop a novel top-down strategy for creating biofunctional nanovesicles for targeted drug delivery.
• To investigate the potential of neutrophil-derived nanovesicles for treating vascular inflammation.

Main Methods:

• Utilized nitrogen cavitation to disrupt activated neutrophils, generating cell membrane nanovesicles.
• Employed intravital microscopy in live mouse models to assess nanovesicle binding to inflamed vasculature.
• Loaded nanovesicles with a NF-κB inhibitor (TPCA-1) for therapeutic evaluation.

Main Results:

• Neutrophil-derived nanovesicles selectively bound to inflamed vasculature via intact integrin β2 molecules.
• TPCA-1-loaded nanovesicles significantly mitigated acute lung inflammation in mice.
• Demonstrated a viable top-down approach for producing targeted drug delivery systems.

Conclusions:

• A novel top-down strategy for generating targeted nanovesicles from diseased tissue was established.
• Neutrophil-derived nanovesicles show promise as a drug delivery platform for vascular inflammation.
• This approach offers potential applications for treating various inflammatory diseases.