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Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys

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  • Alexandra S. Piotrowski-Daspit

    (Yale University
    University of Michigan
    University of Michigan)

  • Laura G. Bracaglia

    (Yale University
    Villanova University)

  • David A. Eaton

    (Yale University)

  • Owen Richfield

    (Yale University)

  • Thomas C. Binns

    (Yale University
    Yale School of Medicine)

  • Claire Albert

    (Yale University)

  • Jared Gould

    (Yale University)

  • Ryland D. Mortlock

    (Yale University)

  • Marie E. Egan

    (Yale School of Medicine
    Yale School of Medicine)

  • Jordan S. Pober

    (Yale School of Medicine
    Yale School of Medicine)

  • W. Mark Saltzman

    (Yale University
    Yale School of Medicine
    Yale School of Medicine
    Yale University)

Abstract

The in vivo efficacy of polymeric nanoparticles (NPs) is dependent on their pharmacokinetics, including time in circulation and tissue tropism. Here we explore the structure-function relationships guiding physiological fate of a library of poly(amine-co-ester) (PACE) NPs with different compositions and surface properties. We find that circulation half-life as well as tissue and cell-type tropism is dependent on polymer chemistry, vehicle characteristics, dosing, and strategic co-administration of distribution modifiers, suggesting that physiological fate can be optimized by adjusting these parameters. Our high-throughput quantitative microscopy-based platform to measure the concentration of nanomedicines in the blood combined with detailed biodistribution assessments and pharmacokinetic modeling provides valuable insight into the dynamic in vivo behavior of these polymer NPs. Our results suggest that PACE NPs—and perhaps other NPs—can be designed with tunable properties to achieve desired tissue tropism for the in vivo delivery of nucleic acid therapeutics. These findings can guide the rational design of more effective nucleic acid delivery vehicles for in vivo applications.

Suggested Citation

  • Alexandra S. Piotrowski-Daspit & Laura G. Bracaglia & David A. Eaton & Owen Richfield & Thomas C. Binns & Claire Albert & Jared Gould & Ryland D. Mortlock & Marie E. Egan & Jordan S. Pober & W. Mark S, 2024. "Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48442-7
    DOI: 10.1038/s41467-024-48442-7
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    References listed on IDEAS

    as
    1. C. Albert & L. Bracaglia & A. Koide & J. DiRito & T. Lysyy & L. Harkins & C. Edwards & O. Richfield & J. Grundler & K. Zhou & E. Denbaum & G. Ketavarapu & T. Hattori & S. Perincheri & J. Langford & A., 2022. "Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Jiajia Cui & Lingfeng Qin & Junwei Zhang & Parwiz Abrahimi & Hong Li & Guangxin Li & Gregory T. Tietjen & George Tellides & Jordan S. Pober & W. Mark Saltzman, 2017. "Ex vivo pretreatment of human vessels with siRNA nanoparticles provides protein silencing in endothelial cells," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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