Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder
Abstract The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain‐lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-05-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202104286 |
| _version_ | 1811235382645227520 |
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| author | Xueqin He Jiang Xie Jing Zhang Xiaorong Wang Xufeng Jia Heng Yin Zhongqing Qiu Zhihang Yang Jiao Chen Zhiliang Ji Wenqi Yu Meiwan Chen Wenming Xu Huile Gao |
| author_facet | Xueqin He Jiang Xie Jing Zhang Xiaorong Wang Xufeng Jia Heng Yin Zhongqing Qiu Zhihang Yang Jiao Chen Zhiliang Ji Wenqi Yu Meiwan Chen Wenming Xu Huile Gao |
| author_sort | Xueqin He |
| collection | DOAJ |
| description | Abstract The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain‐lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin‐triggered lipoxin A4 is a potent anti‐inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood–brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome. As a result, the mitochondrial oxidative stress, DNA damage, and inflammation of microglial cells are prominently alleviated. After the treatment of Asp@TMNPs, the social interaction, stereotype behavior, and anxious condition of ASD mice are notably improved and the activation of microglial cells is inhibited. Overall, this system successively penetrates the BBB and targets microglial cells, therefore, it significantly enhances the intracephalic drug accumulation and improves anti‐neuroinflammatory efficacy of aspirin, providing a promising strategy for ASD treatment. |
| first_indexed | 2024-04-12T11:49:56Z |
| format | Article |
| id | doaj.art-e3d84d17b67746c9b12e4d55c4d2d13c |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-12T11:49:56Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-e3d84d17b67746c9b12e4d55c4d2d13c2022-12-22T03:34:13ZengWileyAdvanced Science2198-38442022-05-01914n/an/a10.1002/advs.202104286Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum DisorderXueqin He0Jiang Xie1Jing Zhang2Xiaorong Wang3Xufeng Jia4Heng Yin5Zhongqing Qiu6Zhihang Yang7Jiao Chen8Zhiliang Ji9Wenqi Yu10Meiwan Chen11Wenming Xu12Huile Gao13Key Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaState Key Laboratory of Stress Cell Biology School of Life Sciences Xiamen University Xiamen 361102 ChinaState Key Laboratory of Stress Cell Biology School of Life Sciences Xiamen University Xiamen 361102 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaState Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macau 999078 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaKey Laboratory of Drug‐Targeting and Drug Delivery of MOE, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second University Hospital West China School of Pharmacy Sichuan University Chengdu 610041 ChinaAbstract The treatment of autism spectrum disorder (ASD) is one of the most difficult challenges in neurodevelopmental diseases, because of the unclear pathogenesis research and low brain‐lesion targeting efficiency. Besides, maternal immune activation has been reported as the most mature and widely used model of ASD and aspirin‐triggered lipoxin A4 is a potent anti‐inflammatory mediator being involved in the resolution of neuroinflammation in ASD. Therefore, an aspirin encapsulated cascade drug delivery system (Asp@TMNPs) is established, which can successively target the blood–brain barrier (BBB) and microglial cells and response to the acid microenvironment in lysosome. As a result, the mitochondrial oxidative stress, DNA damage, and inflammation of microglial cells are prominently alleviated. After the treatment of Asp@TMNPs, the social interaction, stereotype behavior, and anxious condition of ASD mice are notably improved and the activation of microglial cells is inhibited. Overall, this system successively penetrates the BBB and targets microglial cells, therefore, it significantly enhances the intracephalic drug accumulation and improves anti‐neuroinflammatory efficacy of aspirin, providing a promising strategy for ASD treatment.https://doi.org/10.1002/advs.202104286aspirinautism spectrum disordernanoparticlesneuro‐inflammation |
| spellingShingle | Xueqin He Jiang Xie Jing Zhang Xiaorong Wang Xufeng Jia Heng Yin Zhongqing Qiu Zhihang Yang Jiao Chen Zhiliang Ji Wenqi Yu Meiwan Chen Wenming Xu Huile Gao Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder Advanced Science aspirin autism spectrum disorder nanoparticles neuro‐inflammation |
| title | Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder |
| title_full | Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder |
| title_fullStr | Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder |
| title_full_unstemmed | Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder |
| title_short | Acid‐Responsive Dual‐Targeted Nanoparticles Encapsulated Aspirin Rescue the Immune Activation and Phenotype in Autism Spectrum Disorder |
| title_sort | acid responsive dual targeted nanoparticles encapsulated aspirin rescue the immune activation and phenotype in autism spectrum disorder |
| topic | aspirin autism spectrum disorder nanoparticles neuro‐inflammation |
| url | https://doi.org/10.1002/advs.202104286 |
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