Modified bone marrow mesenchymal stem cells derived exosomes loaded with MiRNA ameliorates non-small cell lung cancer

Mingjun Yang, Wen Zhou, Xiao Han, Mingming Xu, Zhipeng Wang, Min Shi, Yanyan Shi, Yunchi Yu
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Abstract

The study aimed to reveal the function of LXY30 peptide-modified bone marrow mesenchymal stem cell-derived exosomes (LXY30-Exos) in NSCLC. LXY30 peptide is a peptide ligand targeting α3β1 integrin, and LXY30 specifically binds to Exos derived from different cells. We use transmission electron microscopy to identify LXY30-Exos and tracking analysis for particles, and the LXY30-Exos internalized by NSCLC cells in vitro and targeted NSCLC tumours in vivo were verified by multiple molecular technologies. The functions of LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 were assessed using cell proliferation, migration and cell apoptosis assays. Meanwhile, the safety of the above engineered Exos was evaluated in vivo. After LXY30-Exos were isolated and identified, LXY30-Exos were confirmed to be internalized by NSCLC cells in vitro and specifically targeted NSCLC tumours in vivo. Functionally, LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 weakened the proliferation, migration and cell cycle of NSCLC cells induced cellular apoptosis in vitro and restrained the tumour progression in vivo. Meanwhile, the safety of LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 was confirmed in vivo. Overall, miR-30c, miR-181b and miR-613 encapsulated in LXY30 peptide-modified BMSC-Exos relieved NSCLC.

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含有 MiRNA 的改良骨髓间充质干细胞衍生外泌体可改善非小细胞肺癌病情
该研究旨在揭示LXY30肽修饰的骨髓间充质干细胞衍生外泌体(LXY30-Exos)在NSCLC中的功能。LXY30肽是一种靶向α3β1整合素的肽配体,LXY30能特异性地与来自不同细胞的外泌体结合。我们利用透射电子显微镜识别LXY30-Exos,并对颗粒进行追踪分析,通过多种分子技术验证了体外NSCLC细胞内化的LXY30-Exos和体内靶向NSCLC肿瘤的LXY30-Exos。利用细胞增殖、迁移和细胞凋亡实验评估了封装了 miR-30c、miR-181b 或 miR-613 的 LXY30-Exos 的功能。同时,对上述工程化 Exos 的安全性进行了体内评估。在分离和鉴定 LXY30-Exos 后,证实 LXY30-Exos 在体外可被 NSCLC 细胞内化,在体内可特异性靶向 NSCLC 肿瘤。从功能上讲,LXY30-Exos包裹的miR-30c、miR-181b或miR-613在体外能削弱NSCLC细胞的增殖、迁移和细胞周期,诱导细胞凋亡,在体内能抑制肿瘤的进展。同时,LXY30-Exos封装的miR-30c、miR-181b或miR-613在体内的安全性也得到了证实。总之,LXY30多肽修饰的BMSC-Exos中包裹的miR-30c、miR-181b和miR-613可缓解NSCLC。
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期刊介绍: The Journal of Cellular and Molecular Medicine serves as a bridge between physiology and cellular medicine, as well as molecular biology and molecular therapeutics. With a 20-year history, the journal adopts an interdisciplinary approach to showcase innovative discoveries. It publishes research aimed at advancing the collective understanding of the cellular and molecular mechanisms underlying diseases. The journal emphasizes translational studies that translate this knowledge into therapeutic strategies. Being fully open access, the journal is accessible to all readers.
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