A microRNA delivery carrier for hepatic carcinoma therapy using layer-by-layer self-assembled mesenchymal stem cells

Background: Several microRNAs (miRNAs), such as miR101, have been reported to be effective for hepatocellular carcinoma (HCC) therapy in preclinical studies; while its further application is hampered due to the lack of desirable delivery systems. Based on the characteristics of mesenchymal stem cells (MSCs), including good biocompatibility and tropism to HCC, the current study was designed to investigate whether miR101-loaded MSCs (miR101-MSCs) using layer-by layer (LbL) self-assembled gelatin and alginate could target the delivery of miR101 to HCC. Methods: The characterization of miR101-loaded MSCs was determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Zeta potential analysis. The tropism and of miR101-MSCs to HCC were detected by Transwell chamber assay, and the anti-tumor potential of miR101-MSCs against HCC was examined by Annexin V-FITC/PI staining, BrdU incorporation assay, and immunoblotting with antibodies against proliferating cell nuclear antigen (PCNA) and caspase-3. Results: The results showed that a thin LbL film containing miR101 was encapsulated on the surface of MSCs. Furthermore, miR101-loaded MSCs had a tropism to hepatoma cells. Finally, treatment of BEL-7402 cells, an HCC cell line, with miR101-loaded MSCs led to significant proliferation inhibition and apoptosis of BEL-7402 cells. Conclusions: These in vitro findings suggest that MSCs loaded with miRNA by LbL self-assembly may be a promising and minimally invasive approach for targeted treatment of HCC.