Exosome-mediated microRNA-497 delivery for anti-cancer therapy in a microfluidic 3D lung cancer model

Abstract

A 3D cell culture system that mimics the lung cancer microenvironment was used to investigate the effect of exosomes encapsulating miR-497 on tumor growth and angiogenesis, and could be a predictive, cost-efficient translational tool to develop targeted cancer therapy.

Hepatoma-Derived Growth Factor: An Overview and Its Role as a Potential Therapeutic Target Molecule for Digestive Malignancies

“…The fact that HDGF is a representative member of a gene family ( Figure 1; Figure 2) might be advantageous when we consider it as a therapeutic target. Recently, the significant roles of HDGF in malignant diseases were reported for many non-digestive malignant diseases, including osteosarcoma [61,62], endometrial cancer [63,64], lung cancer [65][66][67], malignant glioma [68][69][70], cervical cancer [71], ovarian cancer [72] and breast cancer [73]. Thus, HDGF is considered as a potential target molecule for anticancer therapy.…”

“…Recently, non-coding RNAs, such as microRNAs and long non-coding RNAs (lncRNAs), which modulate the function of the target genes, have been shown to have an important role in several diseases [77,78]. Indeed, various microRNAs [40,61,62,[64][65][66][67]69,72] and lncRNAs [49,61,69,71,73] have been suggested to be involved in the regulation of the functions of HDGF, findings that may support the development of HDGF-targeting therapies. For instance, lncRNA HLA complex P5 (lnc HCP5) was reported to cause gemcitabine resistance in pancreatic cancer cells, through the upregulation of miR-214-3p and its target gene, HDGF [40].…”

In vivo gene delivery mediated by non-viral vectors for cancer therapy

“…More recently, delivery and controlled regulation of genes via exosomes is recognized as a potential therapeutic method in the treatment of cancer. Researchers have developed an exosome-based microRNA-497 delivery platform for anti-cancer therapy in a microfluidic 3D lung cancer model [164]. In another study, scientists developed MDM2 siRNA loaded triazine-modified dendrimer NPs for gene delivery, which displayed remarkable tumor growth inhibition in the PC9 xenograft tumor model [165].…”

Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies

“…One of the main target genes in angiogenesis is vascular endothelial growth factor (VEGF). miR-100/497 mediated downregulation of this gene leads to a reduction in the growth and spread of lung and breast cancer [ 121 , 122 ]. Specifically, the paracrine effects of miR-100 from MSC-derived EVs in breast cancer cells is indirectly involved in downregulation of VEGF through inhibition of mTOR and a consequent reduction in hypoxia-inducible factor (HIF) 1α [ 121 ].…”

“…Specifically, the paracrine effects of miR-100 from MSC-derived EVs in breast cancer cells is indirectly involved in downregulation of VEGF through inhibition of mTOR and a consequent reduction in hypoxia-inducible factor (HIF) 1α [ 121 ]. Similarly, miR-497-loaded EVs repressed angiogenesis in lung cancer via direct interaction with VEGF-A and other factors, such as YAP1, HDGF, and CCNE1, in a 3D microfluidic device [ 122 ]. Inhibition of angiogenesis was also observed in the treatment of gastric cancer using siRNA against hepatocyte growth factor (HGF); in this case, the EV-siRNA system suppressed not only angiogenesis but also tumor growth, both in vitro and in vivo, through downregulation of HGF and subsequently of VEGF [ 123 ].…”