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

Niu, Shuiqin; Zhang, Lingkun; Zhang, Li; Zhuang, Siyi; Zhan, Xiuyu; Chen, Wuya; Du, Shiwei; Yin, Liang; You, Rong; Li, Chu-Hua; Guan, Yan‐Qing

doi:10.7150/thno.16562

Cited by 126 publications

(55 citation statements)

References 50 publications

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“…In an attempt to establish a promising treatment for PD, researchers developed a nanocarrier composed of Fe3O4 nanoparticles coated with oleic acid molecules and absorbed short hairpin RNA. It was shown that these superparamagnetic nanoparticles reduced the expression of α-synuclein, suppressed its toxic effects on the cells, and blocked α-synuclein-induced cell death [101]. Another study reported the successful delivery of mesenchymal stem cells (MSCs) and improved neurobehavioral assessment when MSCs were incubated with micrometer-sized iron particles and finally administrated them in a PD mouse model by the way of the intranasal route [102].…”

Section: Magnetic Nanoparticlesmentioning

confidence: 99%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices. Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neurodegenerative disease, leading to the development of bradykinesia and tremors of cardinal motor functions ( Figure 2) [3]. PD models specifically show a decrease in dopamine transporters, which are responsible for dopamine uptake by dopaminergic neurons and progression of neuronal communications. Reduced Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neuro...

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Section: Magnetic Nanoparticlesmentioning

confidence: 99%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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“…Gene therapy, which targets the expression of α-synuclein in neurons, is of great concern, and shRNA (short hairpin RNA) has been identified as a promising treatment of PD (Niu et al, 2017). Therefore, researchers coated magnetic Fe 3 O 4 nanoparticles with oleic acid molecules as a nanocarrier and absorbed shRNA.…”

Section: Application Of Iron Oxide Nanoparticles In the Treatment Of Pdmentioning

confidence: 99%

“…Therefore, researchers coated magnetic Fe 3 O 4 nanoparticles with oleic acid molecules as a nanocarrier and absorbed shRNA. They demonstrated that these superparamagnetic nanoparticles can reduce the expression of α-synuclein and thus can prevent the toxic effects on the cell and suppress apoptosis by α-synuclein (Niu et al, 2017). Salama et al (2017) isolated MSCs from C57BL/6 mice, incubated MSCs with micrometer-sized iron oxide (referred to as MPIOs) particles, and finally administrated them in a PD mouse model by the way of the intranasal (IN) route.…”

Section: Application Of Iron Oxide Nanoparticles In the Treatment Of Pdmentioning

confidence: 99%

Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer’s Disease

Luo

Zhu

et al. 2020

Front. Cell. Neurosci.

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“…Inorganic particles possess several of the desirable characteristics for nucleic acid transportation, such as biocompatibility, ease of manufacture and storage, as well as ease of controlling their synthesis. To date, numerous studies have been carried out with this type of inorganic particles such as magnetic particles for miRNA release with different applications like cancer [215] and PD [172,216,217].…”

Section: Inorganic Particlesmentioning

confidence: 99%

The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease

Titze‐de‐Almeida

Soto-Sánchez

Fernández

et al. 2020

Cells

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MicroRNAs (miRNAs) are small double-stranded RNAs that exert a fine-tuning sequence-specific regulation of cell transcriptome. While one unique miRNA regulates hundreds of mRNAs, each mRNA molecule is commonly regulated by various miRNAs that bind to complementary sequences at 3’-untranslated regions for triggering the mechanism of RNA interference. Unfortunately, dysregulated miRNAs play critical roles in many disorders, including Parkinson’s disease (PD), the second most prevalent neurodegenerative disease in the world. Treatment of this slowly, progressive, and yet incurable pathology challenges neurologists. In addition to L-DOPA that restores dopaminergic transmission and ameliorate motor signs (i.e., bradykinesia, rigidity, tremors), patients commonly receive medication for mood disorders and autonomic dysfunctions. However, the effectiveness of L-DOPA declines over time, and the L-DOPA-induced dyskinesias commonly appear and become highly disabling. The discovery of more effective therapies capable of slowing disease progression –a neuroprotective agent–remains a critical need in PD. The present review focus on miRNAs as promising drug targets for PD, examining their role in underlying mechanisms of the disease, the strategies for controlling aberrant expressions, and, finally, the current technologies for translating these small molecules from bench to clinics.

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

Cited by 126 publications

References 50 publications

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer’s Disease

The Promise and Challenges of Developing miRNA-Based Therapeutics for Parkinson’s Disease

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