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Development of a Tau-Targeted Drug Delivery System Using a Multifunctional Nanoscale Metal-Organic Framework for Alzheimer's Disease Therapy.
ACS Appl Mater Interfaces. 2020 Oct 07; 12(40):44447-44458.AA

Abstract

Alzheimer's disease (AD) is a widespread and burdensome neurodegenerative disease; effective diagnostic methods are lacking, and it remains incurable. The clinical applications of nanoscale metal-organic frameworks (NMOFs) have mainly focused on disease diagnosis and treatment of cancer. A multifunctional NMOF-based nanoplatform was successfully developed for the application in AD diagnosis and therapy. The magnetic nanomaterial Fe-MIL-88B-NH2 was selected to encapsulate methylene blue (MB, a tau aggregation inhibitor) and used as a magnetic resonance contrast material. Subsequently, the targeting reagent 5-amino-3-(pyrrolo[2,3-c]pyridin-1-yl)isoquinoline (defluorinated MK6240, DMK6240) was connected to the surface of Fe-MIL-88B-NH2 via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) to enhance hyperphosphorylated tau targeting, resulting in the formation of an advanced drug delivery system, Fe-MIL-88B-NH2-NOTA-DMK6240/MB. The surface properties of Fe-MIL-88B-NH2-NOTA-DMK6240/MB enable outstanding magnetic resonance imaging capability, as well as amelioration of AD symptoms in vitro and in vivo via the inhibition of hyperphosphorylated tau aggregation and impediment of neuronal death. In conclusion, a tau-targeted drug delivery platform with both disease diagnostics and treatment functions was developed in order to promote new applications of MOFs in the fields of AD and has potential applications in other neurodegenerative diseases.

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Authors+Show Affiliations

Zhao J
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Yin F
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Ji L
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Wang C
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Shi C
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Liu X
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Yang H
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Wang X
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Kong L
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.

MeSH

Alzheimer DiseaseAnimalsCognitionDisease Models, AnimalDrug Delivery SystemsHumansMagnetite NanoparticlesMaleMetal-Organic FrameworksMethylene BlueNeuroprotective AgentsParticle SizeProtein AggregatesRatsRats, Sprague-DawleySurface PropertiesTumor Cells, Culturedtau Proteins

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32897042

Citation

Zhao, Jinhua, et al. "Development of a Tau-Targeted Drug Delivery System Using a Multifunctional Nanoscale Metal-Organic Framework for Alzheimer's Disease Therapy." ACS Applied Materials & Interfaces, vol. 12, no. 40, 2020, pp. 44447-44458.
Zhao J, Yin F, Ji L, et al. Development of a Tau-Targeted Drug Delivery System Using a Multifunctional Nanoscale Metal-Organic Framework for Alzheimer's Disease Therapy. ACS Appl Mater Interfaces. 2020;12(40):44447-44458.
Zhao, J., Yin, F., Ji, L., Wang, C., Shi, C., Liu, X., Yang, H., Wang, X., & Kong, L. (2020). Development of a Tau-Targeted Drug Delivery System Using a Multifunctional Nanoscale Metal-Organic Framework for Alzheimer's Disease Therapy. ACS Applied Materials & Interfaces, 12(40), 44447-44458. https://doi.org/10.1021/acsami.0c11064
Zhao J, et al. Development of a Tau-Targeted Drug Delivery System Using a Multifunctional Nanoscale Metal-Organic Framework for Alzheimer's Disease Therapy. ACS Appl Mater Interfaces. 2020 Oct 7;12(40):44447-44458. PubMed PMID: 32897042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of a Tau-Targeted Drug Delivery System Using a Multifunctional Nanoscale Metal-Organic Framework for Alzheimer's Disease Therapy. AU - Zhao,Jinhua, AU - Yin,Fucheng, AU - Ji,Limei, AU - Wang,Cheng, AU - Shi,Cunjian, AU - Liu,Xingchen, AU - Yang,Huali, AU - Wang,Xiaobing, AU - Kong,Lingyi, Y1 - 2020/09/16/ PY - 2020/9/9/pubmed PY - 2021/3/11/medline PY - 2020/9/8/entrez KW - Alzheimer’s disease KW - magnetic resonance imaging KW - metal−organic frameworks KW - targeted drug deliver KW - tauopathy SP - 44447 EP - 44458 JF - ACS applied materials & interfaces JO - ACS Appl Mater Interfaces VL - 12 IS - 40 N2 - Alzheimer's disease (AD) is a widespread and burdensome neurodegenerative disease; effective diagnostic methods are lacking, and it remains incurable. The clinical applications of nanoscale metal-organic frameworks (NMOFs) have mainly focused on disease diagnosis and treatment of cancer. A multifunctional NMOF-based nanoplatform was successfully developed for the application in AD diagnosis and therapy. The magnetic nanomaterial Fe-MIL-88B-NH2 was selected to encapsulate methylene blue (MB, a tau aggregation inhibitor) and used as a magnetic resonance contrast material. Subsequently, the targeting reagent 5-amino-3-(pyrrolo[2,3-c]pyridin-1-yl)isoquinoline (defluorinated MK6240, DMK6240) was connected to the surface of Fe-MIL-88B-NH2 via 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) to enhance hyperphosphorylated tau targeting, resulting in the formation of an advanced drug delivery system, Fe-MIL-88B-NH2-NOTA-DMK6240/MB. The surface properties of Fe-MIL-88B-NH2-NOTA-DMK6240/MB enable outstanding magnetic resonance imaging capability, as well as amelioration of AD symptoms in vitro and in vivo via the inhibition of hyperphosphorylated tau aggregation and impediment of neuronal death. In conclusion, a tau-targeted drug delivery platform with both disease diagnostics and treatment functions was developed in order to promote new applications of MOFs in the fields of AD and has potential applications in other neurodegenerative diseases. SN - 1944-8252 UR - https://www.unboundmedicine.com/medline/citation/32897042/Development_of_a_Tau_Targeted_Drug_Delivery_System_Using_a_Multifunctional_Nanoscale_Metal_Organic_Framework_for_Alzheimer's_Disease_Therapy_ DB - PRIME DP - Unbound Medicine ER -