Characterization of Polyethylene Glycol‐Polyethyleneimine as a Vector for Alpha‐Synuclein siRNA Delivery to PC12 Cells for Parkinson's Disease

Liu, Yunyun; Yang, Xiaoyun; Li, Zhong; Liu, Zhonglin; Cheng, Du; Wang, Yong; Wen, Xiaobin; Hu, Jiefeng; Li, Jun; Wang, Limin; Wang, Huijun

doi:10.1111/cns.12176

Cited by 38 publications

(9 citation statements)

References 46 publications

(47 reference statements)

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“…36 These modifications include the conjugation of PEI with different chemically reactive molecules, such as polysaccharides (chitosan, pullulan, and hyaluronic acid) 37−39 and hydrophobic moieties (cholesterol, cholic acid, and stearic acid), 40−42 as well as poly(ethylene glycol) polymers (PEGs). 43 −45 1.3. Magnetic Nanoscale Carriers for DNA/RNA Delivery and Cell Transfection.…”

Section: Magnetic Inorganic Iron-based Nanoparticlesmentioning

confidence: 99%

Acute in Vivo Toxicity Mitigation of PEI-Coated Maghemite Nanoparticles Using Controlled Oxidation and Surface Modifications toward siRNA Delivery

Israel

Lellouche

Ostrovsky

et al. 2015

ACS Appl. Mater. Interfaces

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A ceric ammonium nitrate (CAN)-based doping step was used for the fabrication of core maghemite nanoparticles (NPs) that enabled the obtainment of colloid particles with a view to a high-level nanoparticle (NP) surface doping by Ce(III/IV). Such doping of Ce(III/IV) cations enables one to exploit their quite rich coordination chemistry for ligand coordinative binding. In fact, they were shown to act as powerful Lewis acid centers for attaching any organic (Lewis base) ligand such as a 25 kDa branched PEI polymer. Resulting conPEI25-CAN-γ-Fe2O3 NPs have been fully characterized before a successful implementation of siRNA loading and cell delivery/gene silencing using a well-known dual luciferase system. This attractive result emphasized their significant potential as an NP platform technology toward additional MRI and/or drug delivery (peptide)-relating end applications. However, due to their high positive charge, PEI polymers can cause severe in vivo toxicity due to their interaction with negatively charged red blood cells (RBC), resulting in RBC aggregation and lysis, leading to thrombosis and, finally, to animal death. In order to mitigate these acute toxic effects, two different types of surface modifications were performed. One modification included the controlled oxidation of 0.1-5% of the PEI amines before or after conjugation to the NPs, using hydrogen peroxide or potassium persulfate. The other type of modification was the addition of a second biocompatible polyanionic polymer to the PEI grafted NPs, based on the concept of a layer-by-layer (LbL) technique. This modification is based on the coordination of another polyanionic polymer on the NPs surface in order to create a combined hybrid PEI and polyanionic polymer nanosystem. In both cases, the surface modification successfully mitigated the NP acute in vivo toxicity, without compromising the silencing efficiency.

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Section: Magnetic Inorganic Iron-based Nanoparticlesmentioning

confidence: 99%

Acute in Vivo Toxicity Mitigation of PEI-Coated Maghemite Nanoparticles Using Controlled Oxidation and Surface Modifications toward siRNA Delivery

Israel

Lellouche

Ostrovsky

et al. 2015

ACS Appl. Mater. Interfaces

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“…A central challenge of gene therapy associated with successful RNA interference involves techniques to efficiently deliver genetic carriers to target cells without inducing significant toxicity and side effects 47. Viral vectors are widely used in gene therapy.…”

Section: Discussionmentioning

confidence: 99%

Inhibition by Multifunctional Magnetic Nanoparticles Loaded with Alpha-Synuclein RNAi Plasmid in a Parkinson's Disease Model

Niu¹,

Zhang²,

Zhang³

et al. 2017

Theranostics

134

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Lewy bodies are considered as the main pathological characteristics of Parkinson's disease (PD). The major component of Lewy bodies is α-synuclein (α-syn). The use of gene therapy that targeting and effectively interfere with the expression of α-syn in neurons has received tremendous attention. In this study, we used magnetic Fe3O4 nanoparticles coated with oleic acid molecules as a nano-carrier. N-isopropylacrylamide derivative (NIPAm-AA) was photo-immobilized onto the oleic acid molecules, and shRNA (short hairpin RNA) was absorbed. The same method was used to absorb nerve growth factor (NGF) to NIPAm-AA to specifically promote neuronal uptake via NGF receptor-mediated endocytosis. Additionally, shRNA plasmid could be released into neurons because of the temperature and pH sensitivity of NIPAm-AA interference with α-syn synthesis. We investigated apoptosis in neurons with abrogated α-syn expression in vitro and in vivo. The results demonstrated that multifunctional superparamagnetic nanoparticles carrying shRNA for α-syn could provide effective repair in a PD model.

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“…Interference RNA (RNAi) is another powerful gene silencing approach, which could be used to inhibit SNCA, PINK, or parkin genes in PD. Recently, the polyethylene glycol-polyethyleneimine (PEG/PEI) siSNCA complex has been transfected into PC12 cells and a significantly decreased SNCA-mRNA expression, preventing MPTP-induced apoptosis [ 205 ]. CRISPR-Cas9 gene editing system.…”

Section: Treatment Of Pdmentioning

confidence: 99%

Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

Maiti

Manna

Dunbar

2017

Transl Neurodegener

395

305

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Gradual degeneration and loss of dopaminergic neurons in the substantia nigra, pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease (PD). In addition, half of the PD patients also exhibit frontostriatal-mediated executive dysfunction, including deficits in attention, short-term working memory, speed of mental processing, and impulsivity. The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients. Because, these therapies neither restore the lost or degenerated dopaminergic neurons, nor prevent or delay the disease progression, the need for more effective therapeutics is critical. In this review, we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD, particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease. The involvement of molecular chaperones, autophagy-lysosomal pathways, and proteasome systems in PD are also highlighted. In addition, emerging therapies, including pharmacological manipulations, surgical procedures, stem cell transplantation, gene therapy, as well as complementary, supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.

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Characterization of Polyethylene Glycol‐Polyethyleneimine as a Vector for Alpha‐Synuclein siRNA Delivery to PC12 Cells for Parkinson's Disease

Cited by 38 publications

References 46 publications

Acute in Vivo Toxicity Mitigation of PEI-Coated Maghemite Nanoparticles Using Controlled Oxidation and Surface Modifications toward siRNA Delivery

Acute in Vivo Toxicity Mitigation of PEI-Coated Maghemite Nanoparticles Using Controlled Oxidation and Surface Modifications toward siRNA Delivery

Inhibition by Multifunctional Magnetic Nanoparticles Loaded with Alpha-Synuclein RNAi Plasmid in a Parkinson's Disease Model

Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

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