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Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome

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Auroliposome represents a highly effective siRNA delivery platform for in vitro and in vivo application. Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of… Click to show full abstract

Auroliposome represents a highly effective siRNA delivery platform for in vitro and in vivo application. Gene silencing using small-interfering RNA (siRNA) is a viable therapeutic approach; however, the lack of effective delivery systems limits its clinical translation. Herein, we doped conventional siRNA-liposomal formulations with gold nanoparticles to create “auroliposomes,” which significantly enhanced gene silencing. We targeted MICU1, a novel glycolytic switch in ovarian cancer, and delivered MICU1-siRNA using three delivery systems—commercial transfection agents, conventional liposomes, and auroliposomes. Low-dose siRNA via transfection or conventional liposomes was ineffective for MICU1 silencing; however, in auroliposomes, the same dose gave >85% gene silencing. Efficacy was evident from both in vitro growth assays of ovarian cancer cells and in vivo tumor growth in human ovarian cell line—and patient-derived xenograft models. Incorporation of gold nanoparticles shifted intracellular uptake pathways such that liposomes avoided degradation within lysosomes. Auroliposomes were nontoxic to vital organs. Therefore, auroliposomes represent a novel siRNA delivery system with superior efficacy for multiple therapeutic applications.

Keywords: delivery; small interfering; efficacy; interfering rna; gene silencing; sirna

Journal Title: Science Advances
Year Published: 2020

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