Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment

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...

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Main Authors: Chenchen Wang, Xiaolei Song, Xiaowan Zhang, Peng Li, Wei Wei, Shihao Sun, Yong Chen
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425004016
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author Chenchen Wang
Xiaolei Song
Xiaowan Zhang
Peng Li
Wei Wei
Shihao Sun
Yong Chen
author_facet Chenchen Wang
Xiaolei Song
Xiaowan Zhang
Peng Li
Wei Wei
Shihao Sun
Yong Chen
author_sort Chenchen Wang
collection DOAJ
description 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 Zn2+ from β-amyloid/Zn2+ (Aβ/Zn2+) polymers, inhibiting Aβ aggregation. Furthermore, small interfering RNA targeting BACE1 was covalently linked to MC to downregulate BACE1 expression. Both in vitro and in vivo 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.
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spelling doaj-art-7f2797803272494bb3ab16ef4b16d0ca2025-08-20T02:28:37ZengElsevierMaterials Today Bio2590-00642025-06-013210184110.1016/j.mtbio.2025.101841Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatmentChenchen Wang0Xiaolei Song1Xiaowan Zhang2Peng Li3Wei Wei4Shihao Sun5Yong Chen6Beijing 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 ChinaJiangsu 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 ChinaJiangsu 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 ChinaBeijing Life Science Academy, Yingcai South 1st Street, Changping District, Beijing, 102200, PR ChinaJiangsu 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; Corresponding author. Southeast University, Nanjing, 210001, PR China.Beijing Life Science Academy, Yingcai South 1st Street, Changping District, Beijing, 102200, PR China; Corresponding author. Beijing Life Science Academy, Beijing, 102200, PR China.Beijing Life Science Academy, Yingcai South 1st Street, Changping District, Beijing, 102200, PR ChinaAlzheimer'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 Zn2+ from β-amyloid/Zn2+ (Aβ/Zn2+) polymers, inhibiting Aβ aggregation. Furthermore, small interfering RNA targeting BACE1 was covalently linked to MC to downregulate BACE1 expression. Both in vitro and in vivo 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.http://www.sciencedirect.com/science/article/pii/S2590006425004016Alzheimer's diseaseMIL/Fe-100Chlorogenic acidAnti-inflammatoryGene silenceBACE1
spellingShingle Chenchen Wang
Xiaolei Song
Xiaowan Zhang
Peng Li
Wei Wei
Shihao Sun
Yong Chen
Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment
Materials Today Bio
Alzheimer's disease
MIL/Fe-100
Chlorogenic acid
Anti-inflammatory
Gene silence
BACE1
title Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment
title_full Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment
title_fullStr Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment
title_full_unstemmed Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment
title_short Multifunctional natural chlorogenic acid based nanocarrier for Alzheimer's disease treatment
title_sort multifunctional natural chlorogenic acid based nanocarrier for alzheimer s disease treatment
topic Alzheimer's disease
MIL/Fe-100
Chlorogenic acid
Anti-inflammatory
Gene silence
BACE1
url http://www.sciencedirect.com/science/article/pii/S2590006425004016
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