Nanomedicine : nanotechnology, biology, and medicine · 2022
Stealth oxime ether lipid vesicles promote delivery of functional DsiRNA in human lung cancer A549 tumor bearing mouse xenografts.
СтатьяПоддержка исследования: вне правительства СШАResearch Support, N.I.H., IntramuralПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Puri Anu, Ibrahim Faisal, O'Reilly Beringhs André, Isemann Camryn, Zakrevsky Paul, Whittenburg Abigail, Hargrove Derek, Kanai Tapan, Dillard Rebecca S, de Val Natalia, Nantz Michael H, Lu Xiuling, Shapiro Bruce A
Аннотация
We previously reported that hydroxylated oxime ether lipids (OELs) efficiently deliver functional Dicer substrate siRNAs (DsiRNAs) in cells. Here, we explored in vivo utility of these OELs, using OEL4 as a prototype and report that surface modification of the OEL4 formulations was essential for their in vivo applications. These surface-modified OEL4 formulations were developed by inclusion of various PEGylated lipids. The vesicle stability and gene knock-down were dependent on the PEG chain length. OEL4 containing DSPE-PEG350 and DSPE-PEG1000 (surprisingly not DSPE2000) promoted gene silencing in cells. In vivo studies demonstrated that OEL4 vesicles formulated using 3 mol% DSPE-PEG350 accumulate in human lung cancer (A549-luc2) xenografts in mice and exhibit a significant increase in tumor to liver ratios. These vesicles also showed a statistically significant reduction of luciferase signal in tumors compared to untreated mice. Taken together, the scalable OEL4:DSPE-PEG350 formulation serves as a novel candidate for delivery of RNAi therapeutics.