Nanogels with covalently bound and releasable trehalose for autophagy stimulation in atherosclerosis.
Nanogels with covalently bound and releasable trehalose for autophagy stimulation in atherosclerosis.
复制标题
具有共价结合和可释放海藻糖的纳米凝胶用于动脉粥样硬化中的自噬刺激。
DOI：
10.1186/s12951-023-02248-9
复制
发表时间：
2023-12-08
影响因子：
10.2
通讯作者：
Wu, Wei
中科院分区：
文献类型：
--
作者：
Zhong, Yuan;Maruf, Ali;Qu, Kai;Milewska, Malgorzata;Wandzik, Ilona;Mou, Nianlian;Cao, Yu;Wu, Wei
动脉粥样硬化是一种复杂的多细胞疾病，是血管疾病的主要原因。在动脉粥样硬化的进展过程中，自噬功能受损，导致脂质积聚介导的泡沫细胞形成。自噬的刺激对于细胞再循环过程的恢复至关重要。其中一种潜在的自噬诱导剂是海藻糖，一种天然存在的非还原性二糖。然而，海藻糖由于其亲水性而导致生物利用度差，这导致通过细胞膜的渗透性差。为了提高其生物利用度，我们开发了海藻糖释放纳米凝胶（TNG）用于治疗动脉粥样硬化。通过6-O-丙烯酰基海藻糖与所选丙烯酰胺型单体的共聚制备纳米凝胶，从而提供高海藻糖缀合（~ 58%，w/w）。TNG显示出相对小的流体动力学直径（dH，67 nm）和均匀的球形形状，并且以负的微电极电位（-18mV）为特征。由于富含海藻糖，TNG在含有血清的生物介质中表现出优异的胶体稳定性，并且对红细胞无溶血性。体外研究证实，TNG可刺激泡沫细胞自噬并增强脂质流出，ApoE−/−小鼠体内研究表明动脉粥样硬化斑块显著减少，同时增加自噬标志物。总之，TNG作为海藻糖递送系统具有很大的前景，可以恢复动脉粥样硬化中受损的自噬介导的脂质流出，从而减少动脉粥样硬化斑块。在线版本包含补充材料，可通过10.1186/s12951-023-02248-9获得。
Atherosclerosis, cholesterol-driven plaque formation in arteries, is a complex multicellular disease which is a leading cause of vascular diseases. During the progression of atherosclerosis, the autophagic function is impaired, resulting in lipid accumulation-mediated foam cell formation. The stimulation of autophagy is crucial for the recovery of cellular recycling process. One of the potential autophagy inducers is trehalose, a naturally occurring non-reducing disaccharide. However, trehalose has poor bioavailability due to its hydrophilic nature which results in poor penetration through cell membranes. To enhance its bioavailability, we developed trehalose-releasing nanogels (TNG) for the treatment of atherosclerosis. The nanogels were fabricated through copolymerization of 6-O-acryloyl-trehalose with the selected acrylamide-type monomers affording a high trehalose conjugation (~ 58%, w/w). TNG showed a relatively small hydrodynamic diameter (dH, 67 nm) and a uniform spherical shape and were characterized by negative ζ potential (-18 mV). Thanks to the trehalose-rich content, TNG demonstrated excellent colloidal stability in biological media containing serum and were non-hemolytic to red blood cells. In vitro study confirmed that TNG could stimulate autophagy in foam cells and enhance lipid efflux and in vivo study in ApoE−/− mice indicated a significant reduction in atherosclerotic plaques, while increasing autophagic markers. In conclusion, TNG hold great promise as a trehalose delivery system to restore impaired autophagy-mediated lipid efflux in atherosclerosis and subsequently reduce atherosclerotic plaques. The online version contains supplementary material available at 10.1186/s12951-023-02248-9.
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DOI：
10.1002/advs.202105875
发表时间：
2022-05
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
通讯作者：
--
影响因子：
81.5
作者：
Libby, Peter;Buring, Julie E.;Lewis, Eldrin F.
通讯作者：
Lewis, Eldrin F.
影响因子：
17.1
作者：
Albanese, Alexandre;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
影响因子：
--
作者：
Maruf, Ali;Milewska, Malgorzata;Wandzik, Ilona
通讯作者：
Wandzik, Ilona
影响因子：
3.3
作者：
Du, Jing;Liang, Yu;Wang, Zhao
通讯作者：
Wang, Zhao