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细菌来源的外膜囊泡,经过过表达的前体 miRNA 工程化修饰,作为用于癌症治疗的递药纳米载体。

Bacteria-derived outer membrane vesicles engineered with over-expressed pre-miRNA as delivery nanocarriers for cancer therapy.

机构信息

School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.

School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.

出版信息

Nanomedicine. 2022 Sep;45:102585. doi: 10.1016/j.nano.2022.102585. Epub 2022 Jul 25.

Abstract

Outer membrane vesicles (OMVs) of Escherichia coli as nanoscale spherical vesicles have been recently used in cancer therapy as drug carriers. However, most of them need complicated methods to load cargos. Herein, we proposed an inexpensive and potentially mass-produced method for the preparation of OMV engineered with over-expressed pre-miRNA. In this work, we found that OMV can be released and inherit over-expressed tRNA from mother E. coli that directly used for the tumor therapy. The eukaryotic cells infection experiments revealed that the over-expressed pre-miRNA inside OMV could be released and processed into mature miRNAs with the aid of the camouflage of "tRNA scaffold". Moreover, the group in vivo treated with targeted OMV obviously inhibited the expression of target oncogenic CXCR4, and significantly restrain the proliferation of breast cancer tissues. Together, these findings indicated that the OMV-based platform is a versatile and powerful strategy for personalized tumor therapy directly and specificity.

摘要

大肠杆菌外膜囊泡(OMVs)作为纳米级球形囊泡,最近已被用于癌症治疗作为药物载体。然而,它们中的大多数需要复杂的方法来装载货物。在此,我们提出了一种廉价且具有潜在大规模生产潜力的方法,用于制备过表达 pre-miRNA 的 OMV。在这项工作中,我们发现 OMV 可以从直接用于肿瘤治疗的过表达 tRNA 的母大肠杆菌中释放并继承。真核细胞感染实验表明,OMV 内部过表达的 pre-miRNA 可以在“tRNA 支架”的伪装下被释放并加工成成熟的 miRNA。此外,用靶向 OMV 处理的动物体内组明显抑制了靶标致癌 CXCR4 的表达,并显著抑制了乳腺癌组织的增殖。总之,这些发现表明基于 OMV 的平台是一种通用且强大的策略,可直接且特异性地用于个性化肿瘤治疗。

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