Enhanced Anti-Atherosclerotic Efficacy of pH-Responsively Releasable Ganglioside GM3 Delivered by Reconstituted High-Density Lipoprotein.
Enhanced Anti-Atherosclerotic Efficacy of pH-Responsively Releasable Ganglioside GM3 Delivered by Reconstituted High-Density Lipoprotein.
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DOI：
10.3390/ijms222413624
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发表时间：
2021-12-20
影响因子：
5.6
通讯作者：
Chen Y
中科院分区：
文献类型：
--
作者：
Rong T;Wei B;Ao M;Zhao H;Li Y;Zhang Y;Qin Y;Zhou J;Zhou F;Chen Y
最近，内源性GM3的动脉粥样硬化保护作用和外源性GM3的动脉粥样硬化抑制作用提示外源性GM3可能被招募作为抗动脉粥样硬化药物。本研究旨在通过重组高密度脂蛋白（rHDL）（一种动脉粥样硬化靶向药物纳米载体）赋予外源性GM3动脉粥样硬化靶向性。制备并表征了无负载rHDL、低浓度负载外源GM3的rHDL （GM3L-rHDL）和相对高浓度负载GM3的rHDL （GM3H-rHDL）。证实了GM3-rHDL对巨噬细胞脂质沉积的抑制作用，且GM3-rHDL不影响红细胞的存活。用高脂饲料喂养ApoE−/−小鼠的体内实验进一步证实了外源性GM3的抗动脉粥样硬化作用，并证明了高密度脂蛋白纳米颗粒（GM3- rhdl）包装的GM3具有增强的抗动脉粥样硬化作用和降低GM3的有效剂量。然后，GM3-rHD的巨噬细胞和动脉粥样硬化斑块靶向能力，很可能是通过GM3-rHDL上的ApoA-I与细胞上的受体（例如SR-B1）的相互作用，分别通过基于微球的方法和基于主动脉碎片的方法得到证实。此外，我们发现溶液酸化增强了GM3- rhdl纳米颗粒的GM3释放，这意味着当GM3- rhdl从中性血液进入酸性动脉粥样硬化斑块时，GM3释放具有ph响应性。rhdl介导的动脉粥样硬化靶向性和GM3- rhdl的ph响应性GM3释放增强了外源性GM3的抗动脉粥样硬化功效。GM3- rhdl纳米颗粒的开发有助于外源性GM3作为临床药物的应用。此外，数据表明GM3-rHDL纳米颗粒有潜力被招募为具有动脉粥样硬化靶向性和增强抗动脉粥样硬化功效的药物纳米载体。
Recently, the atheroprotective role of endogenous GM3 and an atherogenesis-inhibiting effect of exogenous GM3 suggested a possibility of exogenous GM3 being recruited as an anti-atherosclerotic drug. This study seeks to endow exogenous GM3 with atherosclerotic targetability via reconstituted high-density lipoprotein (rHDL), an atherosclerotic targeting drug nanocarrier. Unloaded rHDL, rHDL loaded with exogenous GM3 at a low concentration (GM3L-rHDL), and rHDL carrying GM3 at a relatively high concentration (GM3H-rHDL) were prepared and characterized. The inhibitory effect of GM3-rHDL on lipid deposition in macrophages was confirmed, and GM3-rHDL did not affect the survival of red blood cells. In vivo experiments using ApoE−/− mice fed a high fat diet further confirmed the anti-atherosclerotic efficacy of exogenous GM3 and demonstrated that GM3 packed in HDL nanoparticles (GM3-rHDL) has an enhanced anti-atherosclerotic efficacy and a reduced effective dose of GM3. Then, the macrophage- and atherosclerotic plaque-targeting abilities of GM3-rHD, most likely via the interaction of ApoA-I on GM3-rHDL with its receptors (e.g., SR-B1) on cells, were certified via a microsphere-based method and an aortic fragment-based method, respectively. Moreover, we found that solution acidification enhanced GM3 release from GM3-rHDL nanoparticles, implying the pH-responsive GM3 release when GM3-rHDL enters the acidic atherosclerotic plaques from the neutral blood. The rHDL-mediated atherosclerotic targetability and pH-responsive GM3 release of GM3-rHDL enhanced the anti-atherosclerotic efficacy of exogenous GM3. The development of the GM3-rHDL nanoparticle may help with the application of exogenous GM3 as a clinical drug. Moreover, the data imply that the GM3-rHDL nanoparticle has the potential of being recruited as a drug nanocarrier with atherosclerotic targetability and enhanced anti-atherosclerotic efficacy.
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影响因子：
7
作者：
Mutharasan, R. Kannan;Foit, Linda;Thaxton, C. Shad
通讯作者：
Thaxton, C. Shad
影响因子：
5.3
作者：
Gan, Chaoye;Wang, Zhexuan;Chen, Yong
通讯作者：
Chen, Yong
透明质酸修饰的重组高密度脂蛋白靶向动脉粥样硬化病变
影响因子：
14
作者：
Liu, Lisha;He, Hongliang;Liu, Jianping
通讯作者：
Liu, Jianping
DOI：
10.1111/j.1432-1033.1987.tb13343.x
发表时间：
1987-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
PROKAZOVA, NV;OREKHOV, AN;BERGELSON, LD
通讯作者：
BERGELSON, LD
用原子力显微镜比较研究人天然和修饰脂蛋白颗粒的尺寸和清道夫受体结合
影响因子：
10.2
作者：
Gan C;Wang K;Tang Q;Chen Y
通讯作者：
Chen Y