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Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications

Author

Listed:
  • C. Albert

    (Yale University)

  • L. Bracaglia

    (Yale University)

  • A. Koide

    (New York University Langone Medical Center
    New York University School of Medicine)

  • J. DiRito

    (Yale University)

  • T. Lysyy

    (Yale University)

  • L. Harkins

    (Yale University)

  • C. Edwards

    (Yale University)

  • O. Richfield

    (Yale University
    Yale University)

  • J. Grundler

    (Yale University)

  • K. Zhou

    (Yale University)

  • E. Denbaum

    (New York University Langone Medical Center)

  • G. Ketavarapu

    (New York University Langone Medical Center)

  • T. Hattori

    (New York University Langone Medical Center
    New York University School of Medicine)

  • S. Perincheri

    (Yale University)

  • J. Langford

    (Yale University)

  • A. Feizi

    (Yale University)

  • D. Haakinson

    (Yale University)

  • S. A. Hosgood

    (University of Cambridge)

  • M. L. Nicholson

    (University of Cambridge)

  • J. S. Pober

    (Yale University)

  • W. M. Saltzman

    (Yale University)

  • S. Koide

    (New York University Langone Medical Center
    New York University School of Medicine)

  • G. T. Tietjen

    (Yale University
    Yale University)

Abstract

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33490-8
    DOI: 10.1038/s41467-022-33490-8
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    References listed on IDEAS

    as
    1. Jacob S. Brenner & Daniel C. Pan & Jacob W. Myerson & Oscar A. Marcos-Contreras & Carlos H. Villa & Priyal Patel & Hugh Hekierski & Shampa Chatterjee & Jian-Qin Tao & Hamideh Parhiz & Kartik Bhamidipa, 2018. "Red blood cell-hitchhiking boosts delivery of nanocarriers to chosen organs by orders of magnitude," Nature Communications, Nature, vol. 9(1), pages 1-14, 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.
    3. David Nasralla & Constantin C. Coussios & Hynek Mergental & M. Zeeshan Akhtar & Andrew J. Butler & Carlo D. L. Ceresa & Virginia Chiocchia & Susan J. Dutton & Juan Carlos García-Valdecasas & Nigel Hea, 2018. "A randomized trial of normothermic preservation in liver transplantation," Nature, Nature, vol. 557(7703), pages 50-56, May.
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    Cited by:

    1. Dongkyu Kang & Hyung Shik Kim & Soohyun Han & Yeonju Lee & Young-Pil Kim & Dong Yun Lee & Joonseok Lee, 2023. "A local water molecular-heating strategy for near-infrared long-lifetime imaging-guided photothermal therapy of glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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