Engineered Hybrid Nanovesicles Combining Macrophage Membranes and Artificial Lipids for Abdominal Aortic Aneurysm Therapy.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is a vascular condition with high mortality for which no pharmacological treatments have been approved. Targeting endothelial dysfunction as a primary disease initiator, the vascular endothelial cell (VEC)- protective compound Senkyunolide I (SEI) demonstrates therapeutic promise through robust antiapoptotic activity. Nevertheless, SEI's clinical translation faces limitations due to systemic toxicity, necessitating development of safer therapeutic alternatives.

RESULTS

This study presents an engineered biomimetic nanoplatform (Lipo-MM nanoparticles) combining macrophage-derived membranes with synthetic lipid bilayers for targeted SEI delivery. The macrophage membrane component facilitates precise targeting of activated VECs, while optimized artificial membrane fluidity enhances nanoparticle stability. This dual-membrane configuration enables sustained SEI release with enhanced biodistribution, achieving superior cytoprotective effects. Notably, we established a novel fusion membrane delivery system (Lipo-MM/SEI) and validated its therapeutic efficacy in angiotensin II-challenged AAA murine models. The nanocarrier significantly attenuated AAA progression, reflected by decreased 40% of AAA incidence, 31.4% of maximum aortic diameter, reduced elastin degradation and prevented fatal rupture events. Furthermore, Lipo-MM/SEI administration substantially reduced hepatorenal toxicity associated with free SEI administration during chronic treatment.

CONCLUSION

These results demonstrate that hybrid biomimetic systems integrating natural cellular components with engineered materials offer a strategic approach for vascular endothelial repair therapy while minimizing off-target effects. This membrane fusion technology establishes a prototype for developing next-generation targeted vascular therapeutics.