Gao Weiwei, Yang Nan, Yin Chunyang, Zeng Yi, Zhu Xiaoping
Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Nanjing Medical University, Shanghai 200120, China.
Department of Tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210003, China.
J Oncol. 2022 Jun 6;2022:6141857. doi: 10.1155/2022/6141857. eCollection 2022.
The malignancy of lung cancer (LC) is serious in the world. Exosomes are well-known natural nanovesicles, which are reported to have the potential to carry functional miRNAs as natural carriers and deliver chemotherapeutic drugs. However, the safety and functions of the engineered exosomes for delivering miRNA for the treatment of LC remain to be evaluated. In this study, we found that miR-563 is related to lung cancer from GeneCard database. RT-qPCR and in situ hybridization (ISH) were used to assess miR-563 expression in clinical samples. We prepared and verified the engineered exosomes loaded with miR-563 both and . , flow cytometry, Western blot, and other experimental methods were performed to evaluate the antitumor effect of miR-563 loaded exosomes. In , the LC mouse model was used to observe the effect of the prepared exosomes. The safety of using this exosomes was accessed by liver function test, hematological analysis, and H&E staining in major organs of the mice. Our findings indicated that the miR-563 loaded engineered exosomes inhibit the A549 cells growth , by inhibiting the tumor cell proliferation, migration, and invasion and promoting apoptosis. In , these engineered exosomes were enriched in tumor tissue after injecting to LC model mice and impacted tumor tissue by inhibiting the tumor volume and tumor weight. Importantly, our study indicated that miR-563 loaded engineered exosomes have the potential for clinical application for LC treatment with acceptable safety profiles. Our findings indicate a novel potential therapeutic target for lung cancer patients by miR-563 loaded engineered exosomes.
肺癌（LC）的恶性程度在全球范围内都很严重。外泌体是众所周知的天然纳米囊泡，据报道有潜力作为天然载体携带功能性微小RNA（miRNA）并递送化疗药物。然而，用于递送miRNA治疗肺癌的工程化外泌体的安全性和功能仍有待评估。在本研究中，我们从基因卡数据库中发现miR-563与肺癌有关。采用逆转录定量聚合酶链反应（RT-qPCR）和原位杂交（ISH）来评估临床样本中miR-563的表达。我们制备并验证了负载miR-563的工程化外泌体。采用流式细胞术、蛋白质免疫印迹法和其他实验方法来评估负载miR-563的外泌体的抗肿瘤作用。在体内，利用肺癌小鼠模型观察所制备外泌体的效果。通过肝功能测试、血液学分析以及对小鼠主要器官进行苏木精-伊红（H&E）染色来评估使用这种外泌体的安全性。我们的研究结果表明，负载miR-563的工程化外泌体通过抑制肿瘤细胞增殖、迁移和侵袭以及促进细胞凋亡来抑制A549细胞生长。在体内，将这些工程化外泌体注射到肺癌模型小鼠后，它们在肿瘤组织中富集，并通过抑制肿瘤体积和肿瘤重量来影响肿瘤组织。重要的是，我们的研究表明，负载miR-563的工程化外泌体在具有可接受的安全性的情况下有用于肺癌治疗临床应用的潜力。我们的研究结果表明，负载miR-563的工程化外泌体为肺癌患者提供了一个新的潜在治疗靶点。
