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A cationic amphiphilic co-polymer as a carrier of nucleic acid nanoparticles (Nanps) for controlled gene silencing, immunostimulation, and biodistribution

  1. Author:
    Halman, Justin R
    Kim, Ki-Taek
    Gwak, So-Jung
    Pace, Richard
    Johnson, Morgan Brittany
    Chandler, Morgan R
    Rackley, Lauren
    Viard,Mathias
    Marriott, Ian
    Lee, Jeoung Soo
    Afonin, Kirill A

  2. Author Address

    Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA., Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC, USA., Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC, USA., Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC, USA. Electronic address: ljspia@clemson.edu., Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: kafonin@uncc.edu.,
    1. Year: 2020
    2. Date: Jan
    3. Epub Date: 2019 10 25
  2. Journal: Nanomedicine : nanotechnology, biology, and medicine
    1. 23
    2. Pages: 102094
  4. Type of Article: Article
  5. Article Number: 102094
  6. ISSN: 1549-9634
  1. Abstract:

    Programmable nucleic acid nanoparticles (NANPs) provide controlled coordination of therapeutic nucleic acids (TNAs) and other biological functionalities. Beyond multivalence, recent reports demonstrate that NANP technology can also elicit a specific immune response, adding another layer of customizability to this innovative approach. While the delivery of nucleic acids remains a challenge, new carriers are introduced and tested continuously. Polymeric platforms have proven to be efficient in shielding nucleic acid cargos from nuclease degradation while promoting their delivery and intracellular release. Here, we venture beyond the delivery of conventional TNAs and combine the stable cationic poly-(lactide-co-glycolide)-graft-polyethylenimine with functionalized NANPs. Furthermore, we compare several representative NANPs to assess how their overall structures influence their delivery with the same carrier. An extensive study of various formulations both in vitro and in vivo reveals differences in their immunostimulatory activity, gene silencing efficiency, and biodistribution, with fibrous NANPs advancing for TNA delivery. Copyright © 2019. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.nano.2019.102094
  3. PMID: 31669854
  4. View record in Web of Science®
  5. WOS: 000505029200012
  6. PII : S1549-9634(19)30178-9

Library Notes

  1. Fiscal Year: FY2019-2020
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