Effect of Tumor Suppressor Micro-RNA loaded on Nano-zeolites in Hepatocellular Carcinoma induced mice

Abstract

Several therapeutic approaches are used nowadays for the treatment of patients with HCC. One possible and promising solution is gene therapy that can treat cellular abnormalities by counteracting or correcting the malfunctioning genes within a cancerous cell. MiRNAs are small ( 20–22 nucleotide long ), endogenous, single stranded, noncoding RNA molecules that have emerged as key posttranscriptional modulators of gene expression. Analogous to coding genes, miRNAs are comprised of subsets that can promote tumorigenesis ("Onco-miRs"), or those that inhibit neoplastic transformation (tumor suppressors "TSG-miRs"). Restoration of tumor suppressive miRNAs leads to cell cycle block, increased apoptosis, and reduced tumor angiogenesis and metastasis by inhibiting migration and invasion. Among these miRNAs, miR-34a appears to be particularly important in HCC. Efficient tissue-specific delivery of therapeutic miRNAs is a major challenge for miRNA-based therapy. To circumvent these challenges, several approaches for miRNA delivery have been explored. In the present study, a novel delivery system for miR-34a delivery was prepared. The delivery system composed of branched PEI which electrostaticaly binding to the negatively charged miR-34a construct and adsorbed onto surface-functionalized ZSM-5 zeolite nanoparticles through electrostatic interaction and hydrogen bonding, for the targeted treatment of HCC.