Atherosclerosis (AS) is one of the leading causes of vascular disease, producing high morbidity and mortality in many countries. Autophagy plays an important role when cells are facing serious circumstances, such as oxidative stress induced by Ox-LDL (oxidized low-density lipoprotein). Recent studies have revealed that DEX (dexamethasone acetate) and RAPA (rapamycin) exhibit efficient AS therapeutic ability by protecting endothelial cells and killing foam cells, respectively. Herein, we hypothesize that combining DEX and RAPA together in a specific nanocarrier system can achieve better AS therapy while limiting harmful effects. As a proof of concept, DEX and RAPA coloaded mPEG_2k-DSPE calcium phosphate (CaP) nanoparticles (DR-NPs) were prepared by using a biomineralization method. DR-NPs increased HUVEC survival and induced foam cell apoptosis in vitro, which were correlated with autophagy activity. DR-NPs efficiently aggregated at AS plaques in the carotid artery and abdominal artery in ApoE^{- / -} mice 24 h after i.v. injection. Moreover, DR-NPs exhibited excellent plaque regression ability, with smaller necrotic cores and lipid core areas observed after in vivo treatment. Furthermore, the function of vascular endothelial cells was largely promoted, as evidenced by the dramatically decreased expression levels of adhesion factors, such as MMP-2, MMP-9 and ICAM-1. Consequently, DR-NPs can act as an effective AS therapeutic agent and broaden the AS therapeutic approach by inducing autophagy.

中文翻译：

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醋酸地塞米松和雷帕霉素共载mPEG-DSPE磷酸钙纳米颗粒对动脉粥样硬化的有效治疗。

动脉粥样硬化（AS）是血管疾病的主要原因之一，在许多国家中，其发病率和死亡率很高。当细胞面临严重情况时，例如由Ox-LDL（氧化的低密度脂蛋白）诱导的氧化应激，自噬起着重要的作用。最近的研究表明，DEX（醋酸地塞米松）和RAPA（雷帕霉素）分别通过保护内皮细胞和杀死泡沫细胞表现出有效的AS治疗能力。本文中，我们假设在特定的纳米载体系统中将DEX和RAPA结合在一起可以实现更好的AS治疗，同时限制有害作用。作为概念的证明，DEX和RAPA共载了mPEG _2k通过使用生物矿化方法制备了-DSPE磷酸钙（CaP）纳米颗粒（DR-NP）。DR-NPs增加HUVEC存活并诱导体外泡沫细胞凋亡，这与自噬活性相关。静脉注射后24小时，DR-NPs有效地聚集在ApoE ^-/-小鼠的颈动脉和腹动脉的AS斑块中。此外，DR-NPs表现出优异的斑块消退能力，体内后观察到较小的坏死核心和脂质核心区域治疗。此外，如粘附因子如MMP-2，MMP-9和ICAM-1的表达水平显着降低所证明的，血管内皮细胞的功能被大大促进。因此，DR-NPs可以作为有效的AS治疗剂，并通过诱导自噬而扩展AS治疗方法。