Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer

Abstract

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)–derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery. Graphical Abstract Schematic illustration of the preparation of an exosomal anchor peptide (CP05)-PMO that conjugately binds to exosomes from hUC-MSCs (ePPMO-146b) and the antitumor effect of ePPMO-146b in CRC, which occurs through the inhibition of Smad signaling and epithelial–mesenchymal transition.

The Therapeutic Effects of Blueberry-Treated Stem Cell-Derived Extracellular Vesicles in Ischemic Stroke

“…Studies investigating the use of exosomes have been carried out across a spectrum of diseases, demonstrating their therapeutic potential in conditions such as anticancer effects and ischemic stroke. These findings were used to determine the appropriate concentration of exosomes [ 64 , 65 ]. To assess the effects of EVs in ischemia, we cultured HT22 cells and treated them with A-EVs and B-EVs (1 × 10 10 particles/mL) under OGD.…”

Stem Cell-Derived Exosomes: An Advanced Horizon to Cancer Regenerative Medicine

“…56 miRNA transport via hUC-MSCs inhibits epithelial−mesenchymal transition (EMT) of cancer. 57 Human umbilical cord Wharton's Jelly stem cell (hWJSC) derived exosomes show numerous anticancer effects. 58 In 2000, dental pulp stem cells (DPSCs) derived from human dental pulp were the first dental stem cells (DSCs) to be characterized.…”

“…hUC-MSCs have a significant role in inhibiting cancer cell proliferation and migration . miRNA transport via hUC-MSCs inhibits epithelial–mesenchymal transition (EMT) of cancer . Human umbilical cord Wharton’s Jelly stem cell (hWJSC) derived exosomes show numerous anticancer effects .…”