Liposome-Protamine-DNA Nanoparticle-Mediated Delivery of Short Hairpin RNA Targeting Brachyury Inhibits Chordoma Cell Growth
Recent evidence suggests that brachyury is a crucial molecular driver in the initiation and propagation of chordoma. However, no small molecules have been used to specifically target brachyury. Short hairpin RNA (shRNA) has therapeutic promise for the genetic treatment of cancer, but the usage of shRNA therapeutics is limited by obstacles related to effective delivery into the nuclei of target cancer cells due to their inherent sensitivity to nucleases and large polyanionic characteristics. To overcome instability and low transfection efficiency, liposome-protamine-DNA (LPD) nanoparticles were synthesized and investigated as a non-viral carrier of shRNA targeting brachyury in chordoma cells. The size, zeta potential, affinity and transfection efficiency of LPD-shRNA complexes were characterized, and their biological functions in chordoma cells were evaluated. The transfection efficiency of LPD-shRNA was significant higher than naked shRNA. LPD delivered brachyury shRNA into chordoma cells and inhibited brachyury expression, induced apoptosis, upregulated the epithelial biomarker, E-cadherin, downregulated the mesenchymal biomarker, Snail and Slug, and suppressed cell growth. These data indicate that LPD might be a promising non-viral carrier for shRNA in gene targeted therapy of chordoma.
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Document Type: Research Article
Publication date: October 1, 2016
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