Abstract
Background: Exosomes, as natural intercellular information carriers, have great potential in the field of drug delivery. Many studies have focused on modifying exosome surface proteins to allow drugs to specifically target cancer cells.Methods: In this study, human cord blood mesenchymal stromal cell-derived exosomes were used in the delivery of anti-miRNA oligonucleotides so as to be specifically ingested by tumor cells to perform anti-tumor functions. Mesenchymal stem cells modified by the fusion gene iRGD-Lamp2b were constructed to separate and purify exosomes, and the anti-miRNA-221 oligonucleotide (AMO) was loaded into the exosomes by electroporation.Results: The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells in vitro, and it was further found that AMO-Exos was taken up by tumor cells through interaction with the NRP-1 protein. The results of a xenograft tumor model also showed that iRGD-modified exosomes were obviously enriched in tumor sites, exerting excellent anti-tumor efficacy. In vivo imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues.Conclusion: Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.
Highlights
Anti-microRNA oligonucleotides (AMOs), or anti-miRNAs, bind miRNAs through complementary sequences and inhibit miRNA functions in cancer cells (Rupaimoole and Slack, 2017)
In order to obtain iRGD peptide modified exosomes, plasmids containing the iRGD-Lamp2b fusion gene were further transferred into cbMSCs using lentivirus (Figure 1C)
Exosomes from iRGD-modified cbMSCs were collected and purified, and the AMOs or corresponding NCs were loaded into the exosomes by electric transduction
Summary
Anti-microRNA oligonucleotides (AMOs), or anti-miRNAs, bind miRNAs through complementary sequences and inhibit miRNA functions in cancer cells (Rupaimoole and Slack, 2017). The development of these drugs is based on in-depth descriptions of the biological pathogenesis between target miRNA and diseases (Li and Rana, 2014). Exosome-Mediated Anti-miRNA-221 Delivery to developing miRNA therapeutics is designing a miRNA delivery vector to prevent the degradation of nuclease and the escape of drug molecules from endocytosis (Xie et al, 2018). Many studies have focused on modifying exosome surface proteins to allow drugs to target cancer cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
