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Polyethyleneimine-coated Iron Oxide Nanoparticles as a Vehicle for the Delivery of Small Interfering RNA to Macrophages In Vitro and In Vivo
Published on: February 5, 2019
Polymeric Vector-Mediated Targeted Delivery of Anti-PAK1 siRNA to Macrophages for Efficient Atherosclerosis Treatment
Teng Wu1,2, Hong Xiao2,3, Liejing Lu4
1Department of Hypertension and Vascular Disease, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Abstract:
Atherogenesis, initially induced by endothelial structure alteration and dysfunction, is the main cause of cardiovascular diseases that jeopardize public health. Unfortunately, an efficient strategy for atherosclerosis treatment is still far from satisfying the clinical requirements. Dyslipidemia and chronic inflammatory responses, especially the overexpression of the pro-atherosclerotic factors monocyte chemotactic protein 1 (MCP-1) and interleukin-6 (IL-6) in plaques, represent the key features that promote the development of atherosclerosis. Here, a CD36 antibody-modified small-interfering RNA (siRNA) nanomedicine based on the mPEG-PAsp-(g-PEI) vector was developed for atherosclerosis therapy. In vitro and in vivo studies demonstrated that the synthesized siRNA nanomedicine targeted macrophages, reduced CD36 expression, and inhibited IL-6 and MCP-1 upregulation, and eventually reduced the formation of foam cells and alleviated the pathological process of atherosclerosis. These results indicate that the targeted delivery of anti-PAK1 siRNA using a CD36 antibody-modified polymeric vector represents a novel and efficient strategy for atherosclerosis treatment.
Insights
This study developed novel nanomedicine to target macrophages, reducing key inflammatory factors and foam cell formation. This offers a promising new strategy for treating atherosclerosis and cardiovascular diseases.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Cardiovascular Research
Background:
- Atherosclerosis, a major cause of cardiovascular disease, stems from endothelial dysfunction.
- Current treatments for atherosclerosis are insufficient to meet clinical needs.
- Key drivers of atherosclerosis include dyslipidemia and chronic inflammation, marked by elevated monocyte chemotactic protein 1 (MCP-1) and interleukin-6 (IL-6).
Purpose of the Study:
- To develop and evaluate a novel nanomedicine for targeted atherosclerosis therapy.
- To investigate the efficacy of CD36 antibody-modified siRNA nanomedicine in reducing atherosclerotic progression.
Main Methods:
- A CD36 antibody-modified small-interfering RNA (siRNA) nanomedicine using an mPEG-PAsp-(g-PEI) vector was synthesized.
- In vitro and in vivo studies were conducted to assess the nanomedicine's targeting and therapeutic effects.
- Evaluated macrophage targeting, CD36 expression, and inhibition of IL-6 and MCP-1.
Main Results:
- The synthesized siRNA nanomedicine effectively targeted macrophages.
- CD36 expression was reduced, and IL-6 and MCP-1 upregulation was inhibited.
- Foam cell formation was reduced, and the pathological process of atherosclerosis was alleviated.
Conclusions:
- Targeted delivery of anti-PAK1 siRNA using CD36 antibody-modified polymeric vectors is a novel and effective strategy for atherosclerosis treatment.
- This nanomedicine approach shows potential for advancing cardiovascular disease therapy.
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