IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33490-8.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33490-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33490-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Masataka Kawamura & Catherine Parmentier & Samrat Ray & Sergi Clotet-Freixas & Sharon Leung & Rohan John & Laura Mazilescu & Emmanuel Nogueira & Yuki Noguchi & Toru Goto & Bhranavi Arulratnam & Sujani, 2024. "Normothermic ex vivo kidney perfusion preserves mitochondrial and graft function after warm ischemia and is further enhanced by AP39," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. 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.
    3. 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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. 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.
    2. Ivan V. Zelepukin & Olga Yu. Griaznova & Konstantin G. Shevchenko & Andrey V. Ivanov & Ekaterina V. Baidyuk & Natalia B. Serejnikova & Artur B. Volovetskiy & Sergey M. Deyev & Andrei V. Zvyagin, 2022. "Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Shannon N. Tessier & Reinier J. de Vries & Casie A. Pendexter & Stephanie E. J. Cronin & Sinan Ozer & Ehab O. A. Hafiz & Siavash Raigani & Joao Paulo Oliveira-Costa & Benjamin T. Wilks & Manuela Loper, 2022. "Partial freezing of rat livers extends preservation time by 5-fold," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Adam M. Thorne & Justina C. Wolters & Bianca Lascaris & Silke B. Bodewes & Veerle A. Lantinga & Otto B. Leeuwen & Iris E. M. Jong & Kirill Ustyantsev & Eugene Berezikov & Ton Lisman & Folkert Kuipers , 2023. "Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Zonghu Han & Joseph Sushil Rao & Lakshya Gangwar & Bat-Erdene Namsrai & Jacqueline L. Pasek-Allen & Michael L. Etheridge & Susan M. Wolf & Timothy L. Pruett & John C. Bischof & Erik B. Finger, 2023. "Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33490-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.