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

Autor: Halman JR; Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA., Kim KT; Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC, USA., Gwak SJ; Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC, USA., Pace R; Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC, USA., Johnson MB; Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC, USA., Chandler MR; Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA., Rackley L; Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA., Viard M; Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Marriott I; Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC, USA., Lee JS; Drug Design, Development, and Delivery (4D) Laboratory, Department of Bioengineering, Clemson University, Clemson, SC, USA. Electronic address: ljspia@clemson.edu., Afonin KA; Department of Chemistry, University of North Carolina at Charlotte, Charlotte, NC, USA. Electronic address: kafonin@uncc.edu.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2020 Jan; Vol. 23, pp. 102094. Date of Electronic Publication: 2019 Oct 25.
DOI: 10.1016/j.nano.2019.102094
Abstrakt: 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 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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