Wang Chenchen, Song Xiaolei, Zhang Xiaowan, Li Peng, Wei Wei, Sun Shihao, Chen Yong
Beijing Life Science Academy, Yingcai South 1st Street, Changping District, Beijing, 102200, PR China.
Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Device, Key Laboratory of Environmental Medicine Engineering of Ministry of Education, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, PR China.
Mater Today Bio. 2025 May 8;32:101841. doi: 10.1016/j.mtbio.2025.101841. eCollection 2025 Jun.
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of chlorogenic acid (CHA), a multifunctional natural active compound, in AD therapy by developing a trifunctional nanocarrier (MC-H/R/si). CHA was effectively conjugated with iron-based metal-organic frameworks (MIL/Fe-100) through chelation interaction. The resulting nanocomplex (MC) not only enhances the bioavailability of CHA but also facilitates a synergistic antioxidant effect between CHA and MIL/Fe-100. Importantly, CHA can chelate Zn from β-amyloid/Zn (Aβ/Zn) polymers, inhibiting Aβ aggregation. Furthermore, small interfering RNA targeting BACE1 was covalently linked to MC to downregulate BACE1 expression. Both and experiments revealed that MC-H/R/si effectively scavenges ROS, reduces inflammation and Aβ plaque, and improves the learning and cognitive abilities of APP/PS1 mice. These findings confirm that the trifunctional nanocarrier MC-H/R/si has great potential for AD treatment.
阿尔茨海默病（AD）因其复杂的致病机制和单靶点治疗的有限疗效而带来重大挑战。在本研究中，我们通过开发一种三功能纳米载体（MC-H/R/si），研究了多功能天然活性化合物绿原酸（CHA）在AD治疗中的潜力。CHA通过螯合作用与铁基金属有机框架（MIL/Fe-100）有效结合。所得纳米复合物（MC）不仅提高了CHA的生物利用度，还促进了CHA与MIL/Fe-100之间的协同抗氧化作用。重要的是，CHA可以从β-淀粉样蛋白/锌（Aβ/Zn）聚合物中螯合锌，抑制Aβ聚集。此外，靶向BACE1的小干扰RNA与MC共价连接，以下调BACE1表达。体内和体外实验均表明，MC-H/R/si能有效清除活性氧，减轻炎症和Aβ斑块，并改善APP/PS1小鼠的学习和认知能力。这些发现证实，三功能纳米载体MC-H/R/si在AD治疗中具有巨大潜力。
