Systemic delivery of BACE1 siRNA through neuron-targeted nanocomplexes for treatment of Alzheimer's disease

Wang, Pengzhen; Zheng, Xiaoyao; Guo, Qin; Yang, Peng; Pang, Xiaoying; Qian, Kan; Lü, Wei; Zhang, Qizhi; Jiang, Xinguo

doi:10.1016/j.jconrel.2018.04.034

Cited by 116 publications

(66 citation statements)

References 55 publications

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“…Polymeric NPs are easier to synthesize and scale up and also display low immunogenicity. A pioneering study developed synthesized polymeric nanoplatforms that deliver siRNAs to AD mice brain, but poor in vivo stability and ineffective brain accumulation limit its therapeutic effect (15). Still, more powerful nanomaterials are urgently needed to overcome current poor blood stability and inefficient BBB penetration (42).…”

Section: Discussionmentioning

confidence: 99%

Blood-brain barrier–penetrating siRNA nanomedicine for Alzheimer’s disease therapy

et al. 2020

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Toxic aggregated amyloid-β accumulation is a key pathogenic event in Alzheimer’s disease (AD), which derives from amyloid precursor protein (APP) through sequential cleavage by BACE1 (β-site APP cleavage enzyme 1) and γ-secretase. Small interfering RNAs (siRNAs) show great promise for AD therapy by specific silencing of BACE1. However, lack of effective siRNA brain delivery approaches limits this strategy. Here, we developed a glycosylated “triple-interaction” stabilized polymeric siRNA nanomedicine (Gal-NP@siRNA) to target BACE1 in APP/PS1 transgenic AD mouse model. Gal-NP@siRNA exhibits superior blood stability and can efficiently penetrate the blood-brain barrier (BBB) via glycemia-controlled glucose transporter-1 (Glut1)–mediated transport, thereby ensuring that siRNAs decrease BACE1 expression and modify relative pathways. Noticeably, Gal-NP@siBACE1 administration restored the deterioration of cognitive capacity in AD mice without notable side effects. This “Trojan horse” strategy supports the utility of RNA interference therapy in neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Blood-brain barrier–penetrating siRNA nanomedicine for Alzheimer’s disease therapy

et al. 2020

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“…siRNA against BACE1, an enzyme involved in the amyloidogenic processing, is one of the most studied; beside the lipid based, the most promising nanoformulation is nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) functionalized with CPPs to improve BBB crossing and neuronspecific-targeting. 109,110 These NPs reduced in vivo Aβ plaques, tau hyperphosphorylation and promoted hippocampal neurogenesis and cognitive performance. 110 Tests in vitro and in vivo demonstrated, instead, that liposomes, double functionalized with TfR ligands and a CPP to favor BBB passing improved the therapeutic efficiency of the neuroprotective ApoE2 plasmids.…”

Section: Nutraceutical Loaded Nps and Green Npsmentioning

confidence: 99%

“…109,110 These NPs reduced in vivo Aβ plaques, tau hyperphosphorylation and promoted hippocampal neurogenesis and cognitive performance. 110 Tests in vitro and in vivo demonstrated, instead, that liposomes, double functionalized with TfR ligands and a CPP to favor BBB passing improved the therapeutic efficiency of the neuroprotective ApoE2 plasmids. 108 A very promising and extremely specific approach is represented by antisense oligonucleotides (ASOs), which are small RNA sequences inducing protein repression.…”

Section: Nutraceutical Loaded Nps and Green Npsmentioning

confidence: 99%

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

Binda¹,

Murano²,

Rivolta³

2020

IJN

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The field of nanomedicine is constantly expanding. Since the first work dated in 1999, almost 28 thousand articles have been published, and more and more are published every year: just think that only in the last five years 20,855 have come out (source PUBMED) including original research and reviews. The goal of this review is to present the current knowledge about nanomedicine in Alzheimer's disease, a widespread neurodegenerative disorder in the over 60 population that deeply affects memory and cognition. Thus, after a brief introduction on the pathology and on the state-of-the-art research for NPs passing the BBB, special attention is placed to new targets that can enter the interest of nanoparticle designers and to new promising therapies. The authors performed a literature review limited to the last three years (2017-2020) of available studies with the intention to present only novel formulations or approaches where at least in vitro studies have been performed. This choice was made because, while limiting the sector to nanotechnology applied to Alzheimer, an organic census of all the relevant news is difficult to obtain.

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“…Their work successfully demonstrated the in vitro gene silencing efficiency of the prepared system. Wang et al . developed a PEGylated poly (2‐( N , N ‐dimethylamino) ethyl methacrylate nanoparticle system to deliver BACE1 siRNA.…”

Section: Therapeutic Genes For Cns Diseasesmentioning

confidence: 99%

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

Wang

Huang

2019

The Journal of Gene Medicine

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Gene therapy is a rapidly emerging remedial route for many serious incurable diseases, such as central nervous system (CNS) diseases. Currently, nucleic acid medicines, including DNAs encoding therapeutic or destructive proteins, small interfering RNAs or microRNAs, have been successfully delivered to the CNS with gene delivery vectors using various routes of administration and have subsequently exhibited remarkable therapeutic efficiency. Among these vectors, non‐viral vectors are favorable for delivering genes into the CNS as a result of their many special characteristics, such as low toxicity and pre‐existing immunogenicity, high gene loading efficiency and easy surface modification. In this review, we highlight the main types of therapeutic genes that have been applied in the therapy of CNS diseases and then outline non‐viral gene delivery vectors.

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Systemic delivery of BACE1 siRNA through neuron-targeted nanocomplexes for treatment of Alzheimer's disease

Cited by 116 publications

References 55 publications

Blood-brain barrier–penetrating siRNA nanomedicine for Alzheimer’s disease therapy

Blood-brain barrier–penetrating siRNA nanomedicine for Alzheimer’s disease therapy

<p>Innovative Therapies and Nanomedicine Applications for the Treatment of Alzheimer’s Disease: A State-of-the-Art (2017–2020)</p>

Non‐viral nucleic acid delivery to the central nervous system and brain tumors

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