Reconstitution of microtubule into GTP-responsive nanocapsules

Noriyuki Uchida, Ai Kohata, Kou Okuro, Annalisa Cardellini, Chiara Lionello, Eric A. Zizzi, Marco A. Deriu, Giovanni M. Pavan, Michio Tomishige, Takaaki Hikima and Takuzo Aida ()
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Noriyuki Uchida: RIKEN Center for Emergent Matter Science
Ai Kohata: The University of Tokyo
Kou Okuro: 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
Michio Tomishige: Aoyama Gakuin University
Takaaki Hikima: RIKEN SPring-8 Center
Takuzo Aida: RIKEN Center for Emergent Matter Science

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33156-5

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