The Delivery of Mimic miRNA-7 into Glioblastoma Cells and Tumour Tissue by Graphene Oxide Nanosystems.

IF 4.9 Q2 NANOSCIENCE & NANOTECHNOLOGY Nanotechnology, Science and Applications Pub Date : 2024-09-11 eCollection Date: 2024-01-01 DOI:10.2147/NSA.S469193
Marta Kutwin, Malwina Sosnowska-Ławnicka, Barbara Nasiłowska, Agata Lange, Mateusz Wierzbicki, Sławomir Jaworski
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引用次数: 0

Abstract

Purpose: The use of nanotechnology in medicine has gained attention in developing drug delivery systems. GO has the potential to deliver microRNA (miRNA) mimics or antisense structures. MiRNAs regulate gene expression and their dysregulation is implicated in diseases, including cancer. This study aims to observe changes in morphology, viability, mRNA expression of mTOR/PI3K/Akt and PTEN genes in U87, U118, U251, A172 and T98 glioblastoma cells and xenograft models after GO self-assembly with mimic miRNA-7.

Methods: Colloidal suspension of graphene oxide (GO) was used for obtaining the GO-mimic miRNA-7 nanosystems by self-assembly method. The ultrastructure, size distribution and ATR-FTIR and UV-Vis spectrum were analyzed. The Zeta potential was measured to verify the stability of obtained nanosystem. The entrapment efficiency, loading capacity and released kinetics of mimic miRNA-7 form GO-mimic miRNA-7 nanosystems were analyzed. The transfection efficiency into the glioblastoma cell lines U87, U118, U251, A172 and T98 of mimic miRNA-7 delivered by GO nanosystems was measure by confocal microscopy and flow cytometry. The changes at mRNA expression level of mTOR, PI3K, AKT1 and PTEN genes was measured by qPCR analysis. The xenograft model of U87 and A172 tumour tissue was performed to analyze the effect at tumor size and volume after GO- mimic miRNA-7 nanosystem administration.

Results: The ultrastructure of GO-mimic miRNA-7 nanosystems showed high affinity of mimic miRNA into the GO. The results of transfection efficiency, cell morphology and viability showed that GO -miRNA-7 effectively deliver mimics miRNA-7 into U87, U118, U251, A172 and T98 glioblastoma cells. This approach can reverse miRNA-7 expression's downstream effects and target the mTOR PI3K/Akt pathway observed at gene expression level, reducing xenograft tumour size and volume.

Conclusion: The findings of the study could have significant implications for the development of advanced and precise GO based nanosystems specifically designed for miRNA therapy in cancer treatment.

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利用氧化石墨烯纳米系统向胶质母细胞瘤细胞和肿瘤组织输送模拟 miRNA-7。
目的:纳米技术在医学中的应用已在开发药物输送系统方面获得关注。GO 具有传递微小核糖核酸(miRNA)模拟物或反义结构的潜力。MiRNA 可调控基因表达,其失调与癌症等疾病有关。本研究旨在观察 U87、U118、U251、A172 和 T98 胶质母细胞瘤细胞和异种移植模型在 GO 与模拟 miRNA-7 自组装后的形态、活力、mTOR/PI3K/Akt 和 PTEN 基因的 mRNA 表达变化:方法:利用氧化石墨烯(GO)的胶体悬浮液,通过自组装方法获得GO模拟miRNA-7纳米系统。分析了纳米体系的超微结构、尺寸分布、ATR-FTIR 和 UV-Vis 光谱。测量了 Zeta 电位以验证所获得纳米系统的稳定性。分析了GO-mimic miRNA-7纳米系统对模拟miRNA-7的包埋效率、负载能力和释放动力学。共聚焦显微镜和流式细胞术测定了 GO 纳米系统向胶质母细胞瘤细胞系 U87、U118、U251、A172 和 T98 转染模拟 miRNA-7 的效率。通过 qPCR 分析测定了 mTOR、PI3K、AKT1 和 PTEN 基因 mRNA 表达水平的变化。对U87和A172肿瘤组织进行异种移植模型,分析GO-模拟miRNA-7纳米系统给药后对肿瘤大小和体积的影响:结果:GO-mimic miRNA-7纳米系统的超微结构显示mimic miRNA与GO有很高的亲和力。转染效率、细胞形态和活力结果表明,GO-miRNA-7 纳米系统能有效地将模拟 miRNA-7 导入 U87、U118、U251、A172 和 T98 胶质母细胞瘤细胞。这种方法可以逆转 miRNA-7 表达的下游效应,并在基因表达水平上靶向观察到的 mTOR PI3K/Akt 通路,减少异种移植肿瘤的大小和体积:结论:这项研究的发现对于开发基于 GO 的先进、精确的纳米系统,特别是用于治疗癌症的 miRNA 治疗具有重要意义。
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来源期刊
Nanotechnology, Science and Applications
Nanotechnology, Science and Applications NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
11.70
自引率
0.00%
发文量
3
审稿时长
16 weeks
期刊介绍: Nanotechnology, Science and Applications is an international, peer-reviewed, Open Access journal that focuses on the science of nanotechnology in a wide range of industrial and academic applications. The journal is characterized by the rapid reporting of reviews, original research, and application studies across all sectors, including engineering, optics, bio-medicine, cosmetics, textiles, resource sustainability and science. Applied research into nano-materials, particles, nano-structures and fabrication, diagnostics and analytics, drug delivery and toxicology constitute the primary direction of the journal.
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