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Reconstitution of microtubule into GTP-responsive nanocapsules

Author

Listed:
  • Noriyuki Uchida

    (RIKEN Center for Emergent Matter Science
    Tokyo University of Agriculture and Technology)

  • Ai Kohata

    (The University of Tokyo)

  • Kou Okuro

    (The University of Hong Kong
    The University of Hong Kong)

  • Annalisa Cardellini

    (Politecnico di Torino)

  • Chiara Lionello

    (Politecnico di Torino)

  • Eric A. Zizzi

    (Politecnico di Torino)

  • Marco A. Deriu

    (Politecnico di Torino)

  • Giovanni M. Pavan

    (Politecnico di Torino
    University of Applied Sciences and Arts of Southern Switzerland, Polo Universitario Lugano, Campus Est)

  • Michio Tomishige

    (Aoyama Gakuin University)

  • Takaaki Hikima

    (RIKEN SPring-8 Center)

  • Takuzo Aida

    (RIKEN Center for Emergent Matter Science
    The University of Tokyo)

Abstract

Nanocapsules that collapse in response to guanosine triphosphate (GTP) have the potential as drug carriers for efficiently curing diseases caused by cancer and RNA viruses because GTP is present at high levels in such diseased cells and tissues. However, known GTP-responsive carriers also respond to adenosine triphosphate (ATP), which is abundant in normal cells as well. Here, we report the elaborate reconstitution of microtubule into a nanocapsule that selectively responds to GTP. When the tubulin monomer from microtubule is incubated at 37 °C with a mixture of GTP (17 mol%) and nonhydrolysable GTP* (83 mol%), a tubulin nanosheet forms. Upon addition of photoreactive molecular glue to the resulting dispersion, the nanosheet is transformed into a nanocapsule. Cell death results when a doxorubicin-containing nanocapsule, after photochemically crosslinked for properly stabilizing its shell, is taken up into cancer cells that overexpress GTP.

Suggested Citation

  • Noriyuki Uchida & Ai Kohata & Kou Okuro & Annalisa Cardellini & Chiara Lionello & Eric A. Zizzi & Marco A. Deriu & Giovanni M. Pavan & Michio Tomishige & Takaaki Hikima & Takuzo Aida, 2022. "Reconstitution of microtubule into GTP-responsive nanocapsules," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33156-5
    DOI: 10.1038/s41467-022-33156-5
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    References listed on IDEAS

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