miR-371b-5p-Engineered Exosomes Enhances Tumor Inhibitory Effect

Abstract

Background: Exosomes are well-known natural nanovesicles, that represent one of the recently discovered modes of intercellular communication due to their ability to transmit cellular components. Exosomes have been reported to have potential as natural vectors for carrying functional small RNAs and delivering chemotherapeutic agents to diseased cells. In this study, we aimed to investigate the role of exosomes in carrying miRNA for targeting tumor cells.Methods: We present a novel method for engineering exosomes with functional miR-317b-5b to target tumor cells. MiR-317b-5b exerts its anti-tumor function via its expression in tumors. RT-qPCR was performed to assess the levels of miR-371b-5p, FUT-4. Western blot was performed to measure the levels of CD9, CD81, and FUT-4 proteins. Confocal microscopy was used to observe the internalization of miR-317b-5b in tumor cells. CCK-8, EdU, flow cytometry, wound-healing migration and transwell assays were performed to evaluate cell viability, proliferation, migration, and invasion, respectively.Results: Our findings illustrated that miR-317b-5b-loaded engineered exosomes were internalized by tumor cells. MiR-317b-5b was overexpressed in tumor cells treated with miR-317b-5b-loaded engineered exosomes. The internalization of miR-317b-5b in tumor cells was accompanied by changes of cell viability, proliferation, apoptosis, and migratory and invasive capability. We found that miR-317b-5b-loaded engineered exosomes were presence in tumor tissue sections and miR-317b-5b was overexpressed in tumor tissues of osteosarcoma tumor-bearing mice infected with miR-317b-5b-loaded engineered exosomes. MiR-317b-5b-loaded engineered exosomes had the anti-tumor efficiency in vivo.Conclusion: Our findings show that miR-317b-5b-loaded engineered exosomes can be used as nanocarriers to deliver drug molecules such as miR-317b-5b both in vitro and in vivo to exert its anti-tumor functions.

Engineered Exosomes-Mediated Transfer of hsa-miR-320a Overcomes Chemoresistance in Cervical Cancer Cells via Targeting MCL1

“…Based on the structure, engineered exosomes have become a possibility in the treatment of numerous diseases. A recent study indicated that miR-317b-5b-loaded engineered exosomes can transfer itself both in vitro and in vivo for the anti-tumor functions ( Xue et al, 2021 ). In addition, engineered miR-181b exosomes regulate macrophage polarization, thus to improve osteointegration ( Liu W. et al, 2021 ).…”

Engineered exosomes loaded with miR-494-3p suppress homologous ovarian cancer

“…As for the loading of miRNAs, Xue et al enriched miR-317b-5p in exosomes by using the interaction between TAR and TAT through genetic engineering method (30). Although this automatic loading method has high loading e ciency, the construction of recombinant plasmid is very complicated.…”

Small extracellular vesicles in breast cancer brain metastasis and the prospect of clinical application

“…This can be improved by choosing particular small EVs donors or using bioengineering methods ( Jiang et al, 2022 ). Engineering modifications can greatly improve the targeting ability of small EVs-derived surface proteins and other proteins, improving the therapeutic application of small EVs and increasing their effectiveness for specific drug delivery to the brain ( Xue et al, 2021 ; Jiang et al, 2022 ). New diagnostic platforms and emerging therapeutic strategies will further develop the engineering and therapeutic potential of small EVs in the coming years.…”