期刊
ACS APPLIED NANO MATERIALS
卷 4, 期 11, 页码 11554-11562出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsanm.1c02009
关键词
targeted delivery; nanoparticles; advanced atherosclerosis; vasa vasorum; pigment epithelium-derived factor
资金
- National Natural Science Foundation of China [81773272, 81972886]
- Natural Science Foundation of Shanghai [21ZR1451400]
This study developed a targeting nanodelivery system, cRGD peptide-modified RNPs, for delivering the antiangiogenesis drug PEDF to inhibit neovascularization in plaque. In vitro and in vivo experiments demonstrated the effectiveness of PEDF RNPs in reducing plaque area and thickness, suggesting their potential for future clinical applications in atherosclerosis treatment.
Neovascularization in plaque is the main driving factor for the formation of vulnerable plaque. It is an effective strategy to alleviate atherosclerosis by intervening neovascularization. Herein, we constructed a cRGD peptide (cyclo(Arg-Gly-Asp-D-Phe-Cys))-modified nanodelivery systems (RNPs) for targeted delivery of an antiangiogenesis drug pigment epithelium-derived factor (PEDF), which is known as the strongest endogenous angiogenesis inhibitor. PEDF RNPs have a suitable size and good stability, which is conducive to passive target and long-term blood circulation. In vitro cell uptake study showed that cRGD on the surface of nanoparticles could bind to the overexpressed alpha(nu)beta(3) integrin in HUVECs, resulting in an increased uptake of PEDF RNPs by HUVECs. In vivo targeting experiments indicated that PEDF RNPs could be effectively enriched in plaques by an EPR effect and a cRGD peptide. In an apoE(-/-) mice model of advanced atherosclerosis, we evaluated the therapeutic efficacy of PEDF RNPs by ultrasound imaging. The result indicated that PEDF RNPs can inhibit intimal thickening. Oil Red O (ORO) staining of isolated aorta showed that PEDF RNPs can reduce the area of plaque, compared with free PEDF treatment. H&E (hematoxylin-eosin) and Masson staining of the vessel cross section further proved that PEDF RNPs had a nice curative effect. CD31 staining suggested that the therapeutic effect of PEDF RNPs was related to the inhibition of angiogenesis. This study provides a targeting delivery system for inhibition of vasa vasorum in plaque, which has the potential of clinical application for future atherosclerosis treatment.
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