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- 2018
姜黄素修饰透明质酸的自组装特性及其对Aβ40聚集的抑制作用：透明质酸相对分子质量的影响
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Abstract:
淀粉样β蛋白(amyloid β-peptide, Aβ)的聚集是阿尔兹海默症的主要病因．姜黄素(curcumin, Cur)是一种良好的Aβ聚集小分子抑制剂, 但其存在水溶性和稳定性差等缺点．针对该问题, 笔者先前将Cur修饰在透明质酸(hyaluronic acid, HA)上形成自组装纳米粒子CHA, 不仅改善了Cur的水溶性和稳定性, 而且还提高了Cur对Aβ聚集的抑制效果．为进一步考察HA的相对分子质量对纳米粒子自组装特性及其对Aβ聚集的抑制作用的影响, 本研究将Cur分别以不同修饰度(substitution degree, SD)修饰在相对分子质量40、300和1 000的HA上, 得到3类CHA．实验结果表明：HA相对分子质量能影响CHA的纳米结构及其最佳SD, HA相对分子质量越大, 形成的CHA纳米结构越疏松, 因而其最佳SD越大; 在最佳SD下, 相对分子质量为300的HA自组装形成的CHA的纳米结构最为合适, 其抑制效果最好．研究结果对自组装纳米药物的设计具有重要的参考意义．
The aggregation of amyloid β-peptide(Aβ)is the main cause of Alzheimer’s disease. Curcumin(Cur)is an excellent Aβ aggregation inhibitor but with low solubility and stability. Previously we conjugated Cur to hyaluronic acid(HA)to form self-assembled nanoparticles(CHA)，which not only improved the water solubility and stability of Cur，but also improved its inhibitory effect on Aβ aggregation. In order to further investigate the effect of the relative molecular mass of HA on the self-assembly properties of nanoparticles and the inhibition of Aβ aggregation，Cur was conjugated to three kinds of HA with different relative molecular masses(40，300 and 1 000)at different substitution degrees(SD)to obtain three different classes of CHA. The experimental results revealed that the relative molecular mass of HA could influence the nanostructure of CHA and its optimal SD. Specifically，the larger the relative molecular mass of HA was，the looser the CHA nanostructure was，so the bigger the optimal SD was. Moreover，the CHA assembled by HA with relative molecular mass 300 at the optimal SD had the most appropriate nanostructure，which presented the best inhibitory effect. This study offers important reference value for the design and development of self-assembled nanoparticles
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