Abstract
Background: MicroRNA (abbreviated miRNA)-based treatment holds great promise for application as clinical antitumor therapy, but good carriers for delivery of the miRNA drug are lacking. Exosomes secreted by mesenchymal stem cells (MSCs) have proved to be safe, and exogenously modified exosomes may potentially represent an excellent drug delivery vehicle.Methods: In this study, we designed a delivery nano system using single-stranded variable fragment (scFv)-modified exosomes derived from human cord blood MSCs. Genetic engineering technology was used to obtain anti-Glypican 3 (GPC3) scFv-modified exosomes, which were then loaded with miR-26a mimics through electroporation.Results: Results of electron microscopy and dynamic light scattering indicated that the diameter of the drug-carrying exosomes was about 160 nm. Furthermore, anti-GPC3 scFv-modified exosomes effectively delivered miR-26a to GPC3-positive hepatocellular carcinoma cells, thereby inhibiting cell proliferation and migration by regulating the expression of downstream target genes of miR-26a. The exosomes-based nano system displayed favorable anti-tumor effect in vivo with no obvious side effects.Conclusion: Our data provided a new perspective for the use of exosome delivery systems for miRNA-based antitumor therapy.
Highlights
MicroRNAs are small (20–22 nucleotides) non-coding RNA molecules that bind to partially complementary mRNA sequences and lead to degradation or translation inhibition of target genes (Rottiers and Näär, 2012)
Ectopic expression of the fusion protein occurs at the rough endoplasmic reticulum (ER) and becomes concentrated in lamp2b-enriched exosomes, which are that are stored in a multivesicular bodies (MVB) prior to release from the cell
The exosomes were incorporated into hepatocellular carcinoma (HCC) cells by endocytosis, and the miR-26a mimics were released and bind to the 3’ untranslated regions (UTRs) of its target mRNAs to suppress expression (Figure 1D)
Summary
MicroRNAs (miRNAs) are small (20–22 nucleotides) non-coding RNA molecules that bind to partially complementary mRNA sequences and lead to degradation or translation inhibition of target genes (Rottiers and Näär, 2012). Tumor cells release exosomes, which carry miRNAs, a phenomenon that has be used clinically in tumor diagnostics, tumor cells can absorb miRNAs secreted by donor cells and function as exosome recipient cells (Skog et al, 2008). These data suggest that exosomes are natural carriers for miRNAs and could be used as targeted RNA drug delivery systems. MicroRNA (abbreviated miRNA)-based treatment holds great promise for application as clinical antitumor therapy, but good carriers for delivery of the miRNA drug are lacking. Exosomes secreted by mesenchymal stem cells (MSCs) have proved to be safe, and exogenously modified exosomes may potentially represent an excellent drug delivery vehicle
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
