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Published on: February 5, 2019
Decursin-Loaded Nanovesicles Target Macrophages Driven by the Pathological Process of Atherosclerosis
Hui Chen1,2, Yifeng Zhang3, Mirenuer Aikebaier3
1Department of Endocrinology, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China.
Insights
Decursin, a natural compound, effectively reduces macrophage lipid accumulation and inflammation. A novel nanovesicle delivery system (ALD@EM) enhances decursin
Area of Science:
- Biomedical Engineering
- Pharmacology
- Cardiovascular Research
Background:
- Atherosclerosis (AS) involves macrophage lipid accumulation and inflammation, leading to significant cardiovascular mortality.
- Current treatments for AS have limited efficacy, necessitating novel therapeutic strategies.
- Decursin, a natural compound, demonstrates anti-atherosclerotic properties by inhibiting lipid uptake and inflammatory pathways.
Purpose of the Study:
- To investigate decursin's mechanism in inhibiting macrophage lipid accumulation and inflammation.
- To develop a targeted drug delivery system (ALD@EM) to enhance decursin's efficacy and reduce toxicity in AS treatment.
- To evaluate the therapeutic potential of ALD@EM in reducing atherosclerotic plaque burden.
Main Methods:
- Decursin's inhibitory effects on lipid accumulation and inflammation in macrophages were assessed.
- A targeted nanovesicle system (ALD@EM) was engineered using antibodies (ICAM-1, VCAM-1) and low-density lipoproteins (LDLs).
- The efficacy of ALD@EM in delivering decursin to atherosclerotic plaques and reducing AS pathology was evaluated in vivo.
Main Results:
- Decursin directly interacted with protein kinase Cδ (PKCδ) to inhibit macrophage lipid accumulation and inflammation with low cytotoxicity.
- The ALD@EM system successfully targeted atherosclerotic plaques, enhancing decursin accumulation and therapeutic effects.
- ALD@EM treatment significantly reduced lipid deposition and inflammation in atherosclerotic lesions.
Conclusions:
- Decursin exhibits potent anti-atherosclerotic effects by modulating macrophage responses via PKCδ.
- The ALD@EM nanovesicle system represents a promising targeted delivery strategy for enhancing decursin's therapeutic efficacy in atherosclerosis.
- This approach offers a novel, low-toxicity therapeutic avenue for managing atherosclerotic cardiovascular disease.
Abstract:
Atherosclerosis (AS) is a major pathological factor contributing to the mortality associated with ischemic heart disease and is driven primarily by macrophage-mediated lipid accumulation and inflammatory processes. Conventional cardiovascular pharmacotherapies address these pathological mechanisms but often show limited efficacy, highlighting the need for innovative agents capable of effectively reducing lipid accumulation and inflammation with minimal toxicity. In this study, decursin, a monomer derived from traditional Chinese medicine, is shown to inhibit both lipid accumulation and inflammatory responses in macrophages through direct interaction with protein kinase Cδ (PKCδ), resulting in low cytotoxicity in vitro and negligible toxicity in vivo. To address the short half-life of decursin, a targeted cascade drug delivery system (ALD@EM), which is specifically designed to target AS pathophysiology, is developed. This system employs ICAM-1 and VCAM-1 antibodies for plaque localization and incorporates low-density lipoproteins (LDLs) to facilitate chemotaxis to lesion sites, with an inner layer of apoptotic endothelial cell membranes to increase macrophage internalization and drug release. As a result, ALD@EM nanovesicles significantly increased the accumulation and therapeutic efficacy of decursin within plaques, substantially reducing lipid deposition and plaque inflammation, thereby offering a novel strategy for targeted AS treatment.
