Brain‐Penetration and Neuron‐Targeting DNA Nanoflowers Co‐Delivering miR‐124 and Rutin for Synergistic Therapy of Alzheimer's Disease. Issue 14 (19th February 2022)

• Record Type: Journal Article
• Authors: Ouyang, Qin; Liu, Kai; Zhu, Qubo; Deng, Huiyin; Le, Yuan; Ouyang, Wen; Yan, Xiaoxin; Zhou, Wenhu; Tong, Jianbin
• Is Part Of: Small. Volume 18:Issue 14(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-19
• Subjects: blood–brain barrier -- microRNAs -- nanoparticles -- neurodegenerative diseases -- RVG29 -- β‐amyloid; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202107534
• Languages: English
• ISSNs: 1613-6810

Abstract

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. Abstract : Illustration of the preparation and self‐assembly of multifunctional Rutin@DF‐miR‐124/RVG29 (RDMR) system for Alzheimer's disease (AD) therapy. The RDMR was obtained by DNA self‐assembly, π–π stacking and hybridization. After binding with α7 nAChR, the RDMR can both penetrate the brain–blood barrier and be taken up by neurons. The miR‐124 and Rutin were then released as a neuroprotective factor to improve the AD pathology.