Bioengineered Let-7c Inhibits Orthotopic Hepatocellular Carcinoma and Improves Overall Survival with Minimal Immunogenicity.

摘要: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, warranting better therapies. Restoration tumor-suppressive microRNAs depleted in hepatocellular represents new therapeutic strategy. Herein, we sought to identify potent microRNA (miRNA) agent that could alleviate HCC tumor burden and improve survival. Among collection bioengineered noncoding RNA molecules produced through bacterial fermentation, identified let-7c as the most inhibitor cell viability. Bioengineered selectively modulated target gene expression (Lin-28 homolog B [LIN28B], AT-rich interactive domain-containing protein 3B [ARID3B], lymphoma-extra large [Bcl-xl], c-Myc) cells, consequently induced apoptosis inhibited tumorsphere growth. When formulated with liposomal-branched polyethylenimine polyplex, exhibited serum stability up 24 h. Furthermore, liposomal polyplex-formulated effectively reduce progression orthotopic mouse models, while linear polyethyleneimine-formulated lower degree, revealed by live animal ex vivo tissue imaging studies. This was also supported reduced α-fetoprotein bilirubin levels let-7c-treated mice. In addition, lipopolyplex-formulated extended overall survival tumor-bearing mice elicited no or minimal immune responses healthy immunocompetent human peripheral blood mononuclear cells. These results demonstrate is promising molecule for advanced therapy, polyplex superior modality in vivo delivery.