Engineered Exosomes Loaded with miR-563 Inhibit Lung Cancer Growth

Abstract

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 in vitro and in vivo. In vitro, flow cytometry, Western blot, and other experimental methods were performed to evaluate the antitumor effect of miR-563 loaded exosomes. In in vivo, 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 in vitro, by inhibiting the tumor cell proliferation, migration, and invasion and promoting apoptosis. In in vivo, 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.