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Ultrasound-Aided Targeting Nanoparticles Loaded with miR-181b for Anti-Inflammatory Treatment of TNF-α-Stimulated Endothelial Cells

机译:用miR-181b负载超声辅助靶向纳米颗粒,用于TNF-α刺激的内皮细胞的抗炎治疗

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摘要

Gene therapy is an emerging therapeutic strategy used in clinics. Ultrasound-mediated gene transfection possesses great potential as a secure and available approach for gene delivery. However, transfection efficiency and targeting ability remain challenging. In this study, we developed a kind of ultrasound-aided and targeting nanoparticles for microRNA delivery. These nanoparticles carrying nucleic acids were prepared with cationic poly-(amino acid) encapsulated with perfluoropentane. The formulated nanoparticles were stabilized with negatively charged PGA–PEG–RGD peptide coating. Ultrasound imaging and specific gene transfection using this nanocarrier could be implemented simultaneously. Upon treatment with ultrasound irradiation, phase transition was induced in the nanoparticles and they generated acoustic cavitation, resulting in enhanced gene transfection against the endothelial cells. With the overexpression of miR-181b loaded by the nanoparticles, the TNF-α-stimulated endothelial cells were effectively rescued from the inflammatory state through the protection of cell viability and suppression of cell adhesion.
机译:基因疗法是诊所中使用的新兴治疗策略。超声介导的基因转染具有巨大的潜力作为基因递送的安全和可用方法。然而,转染效率和目标能力仍然具有挑战性。在这项研究中,我们开发了一种用于MicroRNA递送的超声波辅助和靶向纳米粒子。使用包封与全氟化丁烷的阳离子聚(氨基酸)制备携带核酸的这些纳米颗粒。用带负电的PGA-PEG-RGD肽涂层稳定配制的纳米颗粒。使用该纳米载波的超声成像和特定基因转染可以同时实施。在用超声辐射处理时,在纳米颗粒中诱导相转变,并产生声学空化,导致对内皮细胞的增强的基因转染。利用纳米颗粒装载的miR-181b的过表达,通过保护细胞活力和细胞粘附抑制,从炎症状态有效地抵抗TNF-α刺激的内皮细胞。

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