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Brain‐Penetration and Neuron‐Targeting DNA Nanoflowers Co‐Delivering miR‐124 and Rutin for Synergistic Therapy of Alzheimer's Disease

Ouyang, Qin, Liu, Kai, Zhu, Qubo, Deng, Huiyin, Le, Yuan, Ouyang, Wen, Yan, Xiaoxin, Zhou, Wenhu, Tong, Jianbin·2022·Small
DOI 10.1002/smll.202107534
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Abstract

Alzheimer disease (AD) is the leading cause of dementia that affects millions of old people. Despite significant advances in the understanding of AD pathobiology, no disease modifying treatment is available. MicroRNA‐124 (miR‐124) is the most abundant miRNA in the normal brain with great potency to ameliorate AD‐like pathology, while it is deficient in AD brain. Herein, the authors develop a DNA nanoflowers (DFs)‐based delivery system to realize exogenous supplementation of miR‐124 for AD therapy. The DFs with well‐controlled size and morphology are prepared, and a miR‐124 chimera is attached via hybridization. The DFs are further modified with RVG29 peptide to simultaneously realize brain‐blood barrier (BBB) penetration and neuron targeting. Meanwhile, Rutin, a small molecular ancillary drug, is co‐loaded into the DFs structure via its intercalation into the double stranded DNA region. Interestingly, Rutin could synergize miR‐124 to suppress the expression of both BACE1 and APP, thus achieving a robust inhibition of amyloid β generation. The nanosystem could pro‐long miR‐124 circulation in vivo, promote its BBB penetration and neuron targeting, resulting in a significant increase of miR‐124 in the hippocampus of APP/PS1 mice and robust therapeutic efficacy in vivo. Such a bio‐derived therapeutic system shows promise as a biocompatible nanomedicine for AD therapy.

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Metadata

Authors
Ouyang, Q., Liu, K., Zhu, Q., Deng, H., Le, Y., Ouyang, W., Yan, X., Zhou, W., & Tong, J.
Affiliations
  • Hunan Province Key Laboratory of Brain Homeostasis Third Xiangya Hospital Central South University Changsha Hunan 410013 P. R. China
  • Xiangya School of Pharmaceutical Sciences Central South University Changsha Hunan 410013 China
  • Department of Anesthesiology Third Xiangya Hospital Central South University Changsha Hunan 410013 P. R. China
  • Department of Anatomy and Neurobiology Central South University Xiangya School of Medicine Changsha Hunan 410013 China
ORCID
Venue
Small
Publisher
Wiley
Published
2022-02-19
Volume
18
Issue
14
ISSN
  • 1613-6810
  • 1613-6829
DOI
10.1002/smll.202107534
Cited by
94
References
16
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
National Natural Science Foundation of China (81870861, 81471107, 21804144, U1903125, 82073799)

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