RT Journal Article
SR Electronic
T1 Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaba5379
DO 10.1126/sciadv.aba5379
VO 6
IS 30
A1 Hossen, Md. Nazir
A1 Wang, Lin
A1 Chinthalapally, Harisha R.
A1 Robertson, Joe D.
A1 Fung, Kar-Ming
A1 Wilhelm, Stefan
A1 Bieniasz, Magdalena
A1 Bhattacharya, Resham
A1 Mukherjee, Priyabrata
YR 2020
UL http://advances.sciencemag.org/content/6/30/eaba5379.abstract
AB 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.