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Programmable self-regulated molecular buffers for precise sustained drug delivery

Author

Listed:
  • Arnaud Desrosiers

    (Université de Montréal
    Université de Montréal)

  • Rabeb Mouna Derbali

    (Université de Montréal)

  • Sami Hassine

    (Université de Montréal)

  • Jérémie Berdugo

    (Université de Montréal)

  • Valérie Long

    (Université de Montréal
    Institut de Cardiologie de Montréal)

  • Dominic Lauzon

    (Université de Montréal)

  • Vincent De Guire

    (Maisonneuve-Rosemont Hospital, Optilab-CHUM Laboratory Network)

  • Céline Fiset

    (Université de Montréal
    Institut de Cardiologie de Montréal)

  • Luc DesGroseillers

    (Université de Montréal)

  • Jeanne Leblond Chain

    (Univ. Bordeaux, CNRS, INSERM, ARNA)

  • Alexis Vallée-Bélisle

    (Université de Montréal
    Université de Montréal)

Abstract

Unlike artificial nanosystems, biological systems are ideally engineered to respond to their environment. As such, natural molecular buffers ensure precise and quantitative delivery of specific molecules through self-regulated mechanisms based on Le Chatelier’s principle. Here, we apply this principle to design self-regulated nucleic acid molecular buffers for the chemotherapeutic drug doxorubicin and the antimalarial agent quinine. We show that these aptamer-based buffers can be programmed to maintain any specific desired concentration of free drug both in vitro and in vivo and enable the optimization of the chemical stability, partition coefficient, pharmacokinetics and biodistribution of the drug. These programmable buffers can be built from any polymer and should improve patient therapeutic outcome by enhancing drug activity and minimizing adverse effects and dosage frequency.

Suggested Citation

  • Arnaud Desrosiers & Rabeb Mouna Derbali & Sami Hassine & Jérémie Berdugo & Valérie Long & Dominic Lauzon & Vincent De Guire & Céline Fiset & Luc DesGroseillers & Jeanne Leblond Chain & Alexis Vallée-B, 2022. "Programmable self-regulated molecular buffers for precise sustained drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33491-7
    DOI: 10.1038/s41467-022-33491-7
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    References listed on IDEAS

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    1. Jackson S. Turner & Jane A. O’Halloran & Elizaveta Kalaidina & Wooseob Kim & Aaron J. Schmitz & Julian Q. Zhou & Tingting Lei & Mahima Thapa & Rita E. Chen & James Brett Case & Fatima Amanat & Adriana, 2021. "SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses," Nature, Nature, vol. 596(7870), pages 109-113, August.
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    3. Linsley Kelly & Keith E. Maier & Amy Yan & Matthew Levy, 2021. "A comparative analysis of cell surface targeting aptamers," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Teemu Kuosmanen & Johannes Cairns & Robert Noble & Niko Beerenwinkel & Tommi Mononen & Ville Mustonen, 2021. "Drug-induced resistance evolution necessitates less aggressive treatment," PLOS Computational Biology, Public Library of Science, vol. 17(9), pages 1-22, September.
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