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载 microRNA-219 的壳聚糖纳米粒治疗脑胶质母细胞瘤。

MicroRNA-219 loaded chitosan nanoparticles for treatment of glioblastoma.

机构信息

Drug sector, Saudi Food and Drug Authority, Riyadh, Saudi Arabia.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Artif Cells Nanomed Biotechnol. 2022 Dec;50(1):198-207. doi: 10.1080/21691401.2022.2092123.

Abstract

Recent evidence has implicated microRNA-219 (miR-219) in regulation of gene contributed in glioblastoma (GBM) pathogenesis. This study aimed to prepare miR-219 in chitosan (CS) nanoparticles (NPs), characterize and investigate their efficacy on human GBM cell line (U87 MG). NPs were prepared using ionic gelation method. The influence of process parameters on physicochemical characteristics of NPs was investigated. Apoptotic effect of miR-219 was examined on U87 MG cells. Formulated NPs showed particle size of 109 ± 2.18 nm, with poly dispersity index equal to 0.2 ± 0.05, and zeta potential of +20.5 ± 0.7 mV. Entrapment efficiency of miR-219 in loaded NP has reached 95%. The release study demonstrated sustained release pattern of miR-219 from CS-NPs. Gel retardation assay has confirmed the integrity of miR-219 after production process. The fabricated NPs reduced the survival of U87 MG cells to 78% after 24 h of post-transfection, and into 67.5% after 48 h. However, fibroblasts were not affected by the NPs, revealing their specificity for GBM cells. Given the tumour suppressing function of miR-219, and advantage of CS-NPs for gene delivery to the central nervous system, the presented NPs have a great potential for treatment of GBM.

摘要

最近的证据表明,microRNA-219(miR-219)参与了胶质母细胞瘤(GBM)发病机制中基因的调控。本研究旨在制备壳聚糖(CS)纳米粒子(NPs)中的 miR-219,对其进行表征,并研究其对人 GBM 细胞系(U87 MG)的疗效。采用离子凝胶法制备 NPs。考察了工艺参数对 NPs 理化性质的影响。检测了 miR-219 对 U87 MG 细胞的凋亡作用。所制备的 NPs 粒径为 109±2.18nm,多分散指数等于 0.2±0.05,zeta 电位为+20.5±0.7mV。miR-219 的包封效率达到 95%。释放研究表明 CS-NPs 中 miR-219 呈持续释放模式。凝胶阻滞实验证实了 miR-219 在生产过程后的完整性。所制备的 NPs 在转染后 24 小时将 U87 MG 细胞的存活率降低至 78%,48 小时后降低至 67.5%。然而,成纤维细胞不受 NPs 的影响,这表明它们对 GBM 细胞具有特异性。鉴于 miR-219 的肿瘤抑制功能和 CS-NPs 对中枢神经系统基因传递的优势,所提出的 NPs 具有治疗 GBM 的巨大潜力。

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