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载 miRNA 的改良骨髓间充质干细胞来源外泌体改善非小细胞肺癌。

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

机构信息

Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

Department of Thoracic Surgery, Haimen People's Hospital, Nantong, Jiangsu, China.

出版信息

J Cell Mol Med. 2024 Sep;28(18):e70115. doi: 10.1111/jcmm.70115.

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.

摘要

本研究旨在揭示 LXY30 肽修饰的骨髓间充质干细胞衍生的外泌体(LXY30-Exos)在非小细胞肺癌(NSCLC)中的作用。LXY30 肽是一种靶向α3β1 整合素的肽配体,LXY30 特异性结合来自不同细胞的 Exos。我们使用透射电子显微镜鉴定 LXY30-Exos 和颗粒示踪分析,验证了 LXY30-Exos 体外被 NSCLC 细胞内化和体内靶向 NSCLC 肿瘤,并通过多种分子技术进行验证。使用细胞增殖、迁移和细胞凋亡实验评估了 LXY30-Exos 包裹的 miR-30c、miR-181b 或 miR-613 的功能。同时,评估了上述工程化 Exos 在体内的安全性。分离和鉴定 LXY30-Exos 后,确认 LXY30-Exos 体外被 NSCLC 细胞内化,并在体内特异性靶向 NSCLC 肿瘤。功能上,LXY30-Exos 包裹的 miR-30c、miR-181b 或 miR-613 减弱了 NSCLC 细胞的增殖、迁移和细胞周期,诱导细胞凋亡,并在体内抑制肿瘤进展。同时,体内证实了 LXY30-Exos 包裹的 miR-30c、miR-181b 或 miR-613 的安全性。总之,LXY30 肽修饰的 BMSC-Exos 中包裹的 miR-30c、miR-181b 和 miR-613 缓解了 NSCLC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec5d/11423648/760e00fa67d7/JCMM-28-e70115-g002.jpg

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