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Photoactivation of Sulfonated Polyplexes enables localized gene silencing by DsiRNA in breast Cancer cells

  1. Author:
    Puri,Anu
    Viard,Mathias
    Zakrevsky,Paul
    Zampino, Serena
    Chen, Arabella
    Isemann, Camryn
    Alvi, Sohaib
    Clogston,Jeffrey
    Chitgupi, Upendra
    Lovell, Jonathan F
    Shapiro,Bruce

  2. Author Address

    RNA Structure and Design Section, RNA Biology Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: puria@mail.nih.gov., RNA Structure and Design Section, RNA Biology Laboratory, National Cancer Institute, Frederick, MD, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, USA., RNA Structure and Design Section, RNA Biology Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: shapirobr@mail.nih.gov.,
    1. Year: 2020
    2. Date: JUN
    3. Epub Date: 2020 03 06
  2. Journal: Nanomedicine : nanotechnology, biology, and medicine
    1. 26
    2. Pages: 102176
  4. Type of Article: Article
  5. Article Number: 102176
  6. ISSN: 1549-9634
  1. Abstract:

    Translation potential of RNA interference nanotherapeutics remains challenging due to in vivo off-target effects and poor endosomal escape. Here, we developed novel polyplexes for controlled intracellular delivery of dicer substrate siRNA, using a light activation approach. Sulfonated polyethylenimines covalently linked to pyropheophorbide-a for photoactivation and bearing modified amines (sulfo-pyro-PEI) for regulated endosomal escape were investigated. Gene knock-down by the polymer-complexed DsiRNA duplexes (siRNA-NPs) was monitored in breast cancer cells. Surprisingly, sulfo-pyro-PEI/siRNA-NPs failed to downregulate the PLK1 or eGFP proteins. However, photoactivation of these cell associated-polyplexes with a 661-nm laser clearly restored knock-down of both proteins. In contrast, protein down-regulation by non-sulfonated pyro-PEI/siRNA-NPs occurred without any laser treatments, indicating cytoplasmic disposition of DsiRNA followed a common intracellular release mechanism. Therefore, sulfonated pyro-PEI holds potential as a unique trap and release light-controlled delivery platform for on-demand gene silencing bearing minimal off target effects. Copyright © 2020. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.nano.2020.102176
  3. PMID: 32151748
  4. View record in Web of Science®
  5. WOS: 000537257300002
  6. PII : S1549-9634(20)30028-9

Library Notes

  1. Fiscal Year: FY2019-2020
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