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含有左旋多巴和布洛芬并与抗α-突触核蛋白适体偶联的功能化纳米脂质体的多巴胺能和抗神经炎症特性

The Dopaminergic and Anti-Neuroinflammatory Properties of Functionalized Nanoliposomes Containing Levodopa and Ibuprofen and Conjugated with Anti-Alpha-Synuclein Aptamer.

作者信息

Mostafa-Tehrani Sara, Saffari Mostafa, Balali Ebrahim, Khadivi Ramona, Jebali Ali

机构信息

Department of Nanobiomimetics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran.

出版信息

J Neuroimmune Pharmacol. 2025 Jun 9;20(1):66. doi: 10.1007/s11481-025-10227-0.


DOI:10.1007/s11481-025-10227-0
PMID:40489035
Abstract

The purpose of this study was to design, synthesize, characterize, and evaluate the functionalized nanoliposomes containing levodopa and ibuprofen and conjugated with Anti-alpha-synuclein aptamer (FNLLICAASA). In this study, different aptamer sequences were designed and the best aptamer was selected. Then, the FNLLICAASA was synthesized, characterized, and the amount of dopamine level changes in SH-SY5Y cells after exposure to FNLLICAASA was evaluated. Also, the interferon-gamma (INFG) expression was assessed. The binding of FNLLICAASA to SH-SY5Y cells was also investigated using a fluorescent microscope and flow cytometry. The results of molecular docking and molecular dynamics simulation showed that aptamer APT46 with GAGGAG sequence was the best-chosen aptamer. The FNLLICAASA have a size range of 120 to 310 nm with an average positive zeta potential of 30 mV. The dopamine level change was increased in treated SH-SY5Y nerve cells, indicating the dopaminergic property of FNLLICAASA. Also, the expression of INFG was decreased in treated SH-SY5Y nerve cells, indicating the anti-neuroinflammatory property of FNLLICAASA. The binding tests showed the targeted binding of synthesized nanoliposomes to alpha-synuclein molecules on the cell surface of SH-SY5Y cells.

摘要

本研究的目的是设计、合成、表征和评估含有左旋多巴和布洛芬并与抗α-突触核蛋白适配体(FNLLICAASA)偶联的功能化纳米脂质体。在本研究中,设计了不同的适配体序列并选择了最佳适配体。然后,合成并表征了FNLLICAASA,并评估了SH-SY5Y细胞暴露于FNLLICAASA后多巴胺水平的变化量。此外,还评估了γ-干扰素(INFG)的表达。还使用荧光显微镜和流式细胞术研究了FNLLICAASA与SH-SY5Y细胞的结合。分子对接和分子动力学模拟结果表明,具有GAGGAG序列的适配体APT46是最佳选择的适配体。FNLLICAASA的大小范围为120至310nm,平均正ζ电位为30mV。处理后的SH-SY5Y神经细胞中多巴胺水平变化增加,表明FNLLICAASA具有多巴胺能特性。此外,处理后的SH-SY5Y神经细胞中INFG的表达降低,表明FNLLICAASA具有抗神经炎症特性。结合试验表明合成的纳米脂质体与SH-SY5Y细胞表面的α-突触核蛋白分子有靶向结合。

相似文献

[1]
The Dopaminergic and Anti-Neuroinflammatory Properties of Functionalized Nanoliposomes Containing Levodopa and Ibuprofen and Conjugated with Anti-Alpha-Synuclein Aptamer.

J Neuroimmune Pharmacol. 2025-6-9

[2]
Levodopa (L-DOPA) attenuates endoplasmic reticulum stress response and cell death signaling through DRD2 in SH-SY5Y neuronal cells under α-synuclein-induced toxicity.

Neuroscience. 2017-9-1

[3]
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Biochem Biophys Res Commun. 2009-11-11

[4]
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Molecules. 2024-4-13

[5]
[Overexpression of alpha-synuclein in SH-SY5Y cells partially protected against oxidative stress induced by rotenone].

Sheng Li Xue Bao. 2006-10-25

[6]
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Cell Mol Neurobiol. 2008-1

[7]
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Neurotox Res. 2011-7-7

[8]
-acetylcysteine increases dopamine release and prevents the deleterious effects of 6-OHDA on the expression of VMAT2, α-synuclein, and tyrosine hydroxylase.

Neurol Res. 2024-5

[9]
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Pharmacol Rep. 2013

[10]
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Mol Biol Rep. 2020-11

本文引用的文献

[1]
Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies.

Bioorg Chem. 2024-6

[2]
The epidemiology of Parkinson's disease.

Lancet. 2024-1-20

[3]
DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease.

Nat Aging. 2023-10

[4]
Combating Dopaminergic Neurodegeneration in Parkinson's Disease through Nanovesicle Technology.

ACS Chem Neurosci. 2023-8-16

[5]
Novel liposomal formulations for protection and delivery of levodopa: Structure-properties correlation.

Int J Pharm. 2023-8-25

[6]
Therapeutic potential of lipid nanosystems for the treatment of Parkinson's disease.

Ageing Res Rev. 2023-8

[7]
Delivery of Biomimetic Liposomes via Meningeal Lymphatic Vessels Route for Targeted Therapy of Parkinson's Disease.

Research (Wash D C). 2023

[8]
Alpha-synuclein in Parkinson's disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction.

Cell Death Dis. 2023-3-1

[9]
Pathological structural conversion of α-synuclein at the mitochondria induces neuronal toxicity.

Nat Neurosci. 2022-9

[10]
Lipid Nanoparticles: Promising Treatment Approach for Parkinson's Disease.

Int J Mol Sci. 2022-8-19

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