AUTHOR=Han Siqi , Li Guangchao , Jia Meng , Zhao Yulu , He Chenglong , Huang Mengxi , Jiang Longwei , Wu Meijuan , Yang Jiahe , Ji Xiaoqin , Liu Xiaobei , Chen Cheng , Chu Xiaoyuan 

TITLE=Delivery of Anti-miRNA-221 for Colorectal Carcinoma Therapy Using Modified Cord Blood Mesenchymal Stem Cells-Derived Exosomes

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2021.743013

DOI=10.3389/fmolb.2021.743013

ISSN=2296-889X

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> The AMO-loaded exosomes (AMO-Exos) effectively inhibited the proliferation and clonal formation of colon cancer cells <italic>in vitro</italic>, 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. <italic>In vivo</italic> imaging showed that exosomes were mainly distributed in liver, spleen, and lung tissues.</p><p><bold>Conclusion:</bold> Our results suggest that genetically modified exosomes could be an ideal natural nanostructure for anti-miRNA oligonucleotide delivery.</p>