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Multivalent Peptide-Functionalized Bioreducible Polymers for Cellular Delivery of Various RNAs

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    Multivalent Peptide-Functionalized Bioreducible Polymers for Cellular Delivery of Various RNAs
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    • Dong-Chu Yang
      Dong-Chu Yang
      Department of Chemistry, University of California, 1102 Natural Sciences 2, Irvine, California 92697-2025, United States
      More by Dong-Chu Yang
    • Alexander C. Eldredge
      Alexander C. Eldredge
      Department of Chemistry, University of California, 1102 Natural Sciences 2, Irvine, California 92697-2025, United States
      More by Alexander C. Eldredge
    • James C. Hickey
      James C. Hickey
      Department of Chemistry, University of California, 1102 Natural Sciences 2, Irvine, California 92697-2025, United States
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    • Hurik Muradyan
      Hurik Muradyan
      Department of Chemistry, University of California, 1102 Natural Sciences 2, Irvine, California 92697-2025, United States
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    • Zhibin Guan*
      Zhibin Guan
      Department of Chemistry, University of California, 1102 Natural Sciences 2, Irvine, California 92697-2025, United States
      *E-mail: [email protected]
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      Orcidhttp://orcid.org/0000-0003-1370-1511
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    Biomacromolecules

    Cite this: Biomacromolecules 2020, 21, 4, 1613–1624
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    https://doi.org/10.1021/acs.biomac.0c00211
    Published February 24, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    RNA-based therapeutics have garnered tremendous attention due to their potential to revolutionize protein replacement therapies, immunotherapy, and treatment of genetic disorders. The lack of safe and efficient RNA delivery methods has significantly hindered the clinical translation and widespread application of RNA-based therapeutics. With differing sizes and structures of therapeutic RNA molecules, a critical challenge of the field is to develop RNA delivery systems that accommodate these variations while retaining high biocompatibility and efficacy. In this study, we developed a series of multivalent peptide-functionalized bioreducible polymers (MPBP) as a safe and efficient delivery vehicle derived from a core polymer backbone for various RNA species. The facile synthesis of MPBPs from a single polymer backbone provides access to numerous polymers with diverse architectures that enable cellular delivery of different RNA cargos. Postfunctionalization with multifunctional peptides enables strong RNA complexation, enhanced cellular uptake, and facilitates endosomal escape of cargo. The high delivery efficiency and low cytotoxicity for various RNA-MPBP nanoparticles in multiple cell lines demonstrates that the MPBP approach is a novel promising vector strategy for future RNA delivery systems.

    Copyright © 2020 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.biomac.0c00211.

    • Experimental details for MPBP vector synthesis and characterization, gel electrophoresis studies, DLS and TEM studies, initial transfection screening conditions, cytotoxicity measurements, and cellular uptake studies and flow cytometry conditions (PDF)

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    Cited By

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    This article is cited by 18 publications.

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    Biomacromolecules

    Cite this: Biomacromolecules 2020, 21, 4, 1613–1624
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.biomac.0c00211
    Published February 24, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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