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A Biomimetic Macrophage-Membrane-Fused Liposomal System Loaded with GVs-HV Recombinant Plasmid for Targeted
Yuelin Zhang1, Wenting Gu1, Kailing Yu1
1School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Insights
This study introduces a novel bio-vesicle for treating atherosclerosis. Ultrasound-triggered Gas Vesicles (GVs) and Hirudin delivered via macrophage membrane/lipid membrane fusion vesicles effectively reduced arterial plaque in mice.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Gene Therapy
Background:
- Cardiovascular disease is a leading global cause of death.
- Atherosclerotic plaques obstruct blood vessels, leading to heart attack and sudden cardiac death.
- Ultrasound-triggered Gas Vesicles (GVs) offer a noninvasive approach for plaque treatment.
Purpose of the Study:
- To develop and evaluate a novel gene delivery system for atherosclerosis treatment.
- To investigate the efficacy of Hirudin-Gas Vesicle Recombinant Plasmid delivered via bio-fusion vesicles.
- To assess the combined therapeutic effects of GVs cavitation and Hirudin.
Main Methods:
- Construction of a Hirudin-Gas Vesicle Recombinant Plasmid.
- Creation of macrophage membrane/lipid membrane fusion bio-vesicles for gene delivery.
- Evaluation of bio-vesicle targeting, transfection efficiency, and therapeutic effects in a mouse model.
Main Results:
- Bio-fusion vesicles successfully targeted inflammatory cells via integrin α4β1.
- The Hirudin-Gas Vesicle Recombinant Plasmid achieved efficient nuclear transfection.
- Ultrasound-triggered GVs broke up plaques, while Hirudin provided anti-inflammatory and lipid-regulating effects, reducing aortic arch plaque area by 17%.
Conclusions:
- GVs-HV@MM-Lipo demonstrates significant anti-atherosclerotic and anti-inflammatory effects with good safety.
- Combined therapy (GVs-HV@MM-Lipo + Ultrasound) achieved further plaque regression and improved hemodynamics.
- This approach presents a new strategy for atherosclerosis treatment.
Abstract:
Background: Cardiovascular disease is one of the leading causes of death worldwide. The presence of atherosclerotic plaques in the arteries leads to continuous growth and obstruction of blood vessels, which ultimately leads to acute myocardial infarction and sudden cardiac death. Ultrasound-triggered GVs cavitation has great potential in plaque treatment due to its noninvasive nature and safety. Methods: In this work, we constructed a Hirudin-Gas Vesicle Recombinant Plasmid to achieve gene delivery using macrophage membrane/lipid membrane fusion bio-vesicles. Results: The bio-fusion vesicles retained the macrophage membrane protein integrin α4β1 to combine with vascular adhesion molecules highly expressed by inflammatory cells to achieve delivery; the Hirudin-Gas Vesicle Recombinant Plasmid could escape lysosomes and enter the nucleus to achieve highly efficient transfection; Hirudin and Gas Vesicles are exocytosed through cleavage peptide and exocytosis peptide, respectively; their pharmacological effects are linked and complementary. Gas vesicles can break up lesion plates with the assistance of in vitro ultrasound, and Hirudin achieves fragment ablation and anti-inflammatory and lipid regulation. Conclusions: GVs-HV@MM-Lipo exerts potent anti-atherosclerotic and anti-inflammatory effects with favorable safety. GVs-HV@Lipo reduces mice aortic arch plaque area by 17%, while GVs-HV@MM-Lipo+US achieves further plaque regression and improved hemodynamics. Our work opens up a new paradigm in the treatment of atherosclerosis with Chinese medicine.
