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

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 tRNALys-pre-miRNA 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 OMVtRNA-pre-miR-126 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.