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Stealth oxime ether lipid vesicles promote delivery of functional DsiRNA in human lung cancer A549 tumor bearing mouse xenografts

  1. Author:
    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

  2. Author Address

    RNA Structure and Design Section, RNA Biology Laboratory, NCI-NIH, Frederick, MD, United States of America. Electronic address: puria@mail.nih.gov., RNA Structure and Design Section, RNA Biology Laboratory, NCI-NIH, Frederick, MD, United States of America; Department of Chemistry, University of Louisville, Louisville, KY, United States of America., School of Pharmacy, University of Connecticut, Storrs, CT, United States of America., Centre for Molecular Microscopy, FNLCR, Leidos Biomedical Research, Inc., Frederick, MD, United States of America., RNA Structure and Design Section, RNA Biology Laboratory, NCI-NIH, Frederick, MD, United States of America. Electronic address: shapirbr@mail.nih.gov.,
    1. Year: 2022
    2. Date: Jun 04
    3. Epub Date: 2022 06 04
  2. Journal: Nanomedicine : nanotechnology, biology, and medicine
    1. Pages: 102572
  4. Type of Article: Article
  5. Article Number: 102572
  1. Abstract:

    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. Copyright © 2021. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.nano.2022.102572
  3. PMID: 35671983
  4. PII : S1549-9634(22)00058-2

Library Notes

  1. Fiscal Year: FY2021-2022
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