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Targeted Atherosclerosis Treatment Using Vascular Cell Adhesion Molecule-1 Targeting Peptide-Engineered Plant-Derived
Chanwoo Choi1, Won Jong Rhee1,2,3
1Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.
Insights
Onion-derived nanovesicles (Onex) engineered with VHPK peptide (V-Onex) target inflamed cells. This novel therapy effectively reduces inflammation and key processes in atherosclerosis, offering a promising new treatment approach.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Atherosclerosis is a complex vascular disease driven by inflammation and lipid accumulation, leading to heart attack and stroke.
- Current treatments for atherosclerosis focus on cholesterol reduction or anticoagulation, failing to address its multifactorial nature.
- There is a need for innovative therapies that target the dynamic pathological processes of atherosclerosis.
Purpose of the Study:
- To develop and evaluate a novel targeted nanovesicle platform, V-Onex, for atherosclerosis therapy.
- To engineer onion-derived extracellular vesicles (Onex) with a VHPK peptide for specific targeting of inflamed endothelial cells.
- To assess the therapeutic potential of V-Onex in modulating key inflammatory and cellular processes in atherosclerosis.
Main Methods:
- Onion-derived extracellular vesicles (Onex) were engineered with the VHPK peptide to create V-Onex, targeting vascular cell adhesion molecule-1 (VCAM-1).
- Biocompatibility and cytotoxicity were evaluated in human umbilical vein endothelial cells (HUVECs) and THP-1 cells.
- The efficacy of V-Onex was assessed by measuring its accumulation in inflamed cells, reduction of inflammatory markers, and inhibition of monocyte-endothelial cell interactions and foam cell formation.
Main Results:
- Engineered V-Onex demonstrated excellent biocompatibility and stability without cytotoxicity.
- V-Onex selectively accumulated in inflamed endothelial cells, significantly reducing inflammatory markers.
- V-Onex suppressed endothelial cell migration, reduced monocyte adhesion, inhibited oxidized LDL uptake, and decreased foam cell formation.
Conclusions:
- V-Onex represents a promising modular targeted nanovesicle platform for atherosclerosis.
- This engineered nanovesicle effectively modulates multiple pathological processes involved in atherosclerotic progression.
- V-Onex holds potential as a novel therapeutic strategy for treating atherosclerosis.
Abstract:
Atherosclerosis is a chronic vascular disease characterized by lipid accumulation, endothelial dysfunction, and persistent inflammation, which can ultimately lead to life-threatening complications, such as myocardial infarction and stroke. Current therapies primarily focus on lowering cholesterol levels or preventing blood clot formation. However, the multifactorial and dynamic nature of atherosclerotic progression is not addressed. We designed a therapeutic platform based on onion-derived extracellular vesicles (Onex), nanovesicles originating from onions with excellent biocompatibility and strong anti-inflammatory effects. Onex was engineered with the VHPK peptide, to construct V-Onex, specifically targeting vascular cell adhesion molecule-1 (VCAM-1), which is strongly upregulated in inflamed endothelial cells during atherosclerosis. Engineered V-Onex exhibited excellent biocompatibility and stability without inducing cytotoxicity in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. V-Onex selectively accumulated in inflamed endothelial cells and significantly reduced the expression of inflammatory markers in HUVECs and THP-1 cells. It also suppresses the migration of endothelial cells and reduces their interaction with monocytes, both of which contribute to plaque formation. In THP-1 cells, V-Onex inhibited the uptake of oxidized low-density lipoprotein and reduced foam cell formation. Collectively, V-Onex is a promising modular targeted nanovesicle platform capable of modulating multiple pathological processes associated with atherosclerosis.
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