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Reconstitution of microtubule into GTP-responsive nanocapsules

Noriyuki Uchida1,2, Ai Kohata3, Kou Okuro4,5

  • 1RIKEN Center for Emergent Matter Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.

Nature Communications
|September 15, 2022
PubMed

Insights

Researchers developed novel nanocapsules that selectively collapse in response to guanosine triphosphate (GTP), offering targeted drug delivery for cancer and RNA virus infections. These GTP-responsive nanocapsules avoid triggering in normal cells, enhancing therapeutic safety.

Area of Science:

  • Biotechnology
  • Materials Science
  • Nanomedicine

Background:

  • Guanosine triphosphate (GTP)-responsive nanocapsules show promise for treating diseases like cancer and RNA viral infections.
  • Existing GTP-responsive carriers also react to adenosine triphosphate (ATP), limiting their specificity as ATP is common in healthy cells.

Purpose of the Study:

  • To engineer a nanocapsule that selectively responds to GTP, not ATP, for improved drug delivery.
  • To utilize microtubule components for creating a novel, GTP-specific nanocarrier system.

Main Methods:

  • Reconstituting tubulin monomers into nanosheets using a specific GTP/GTP* mixture at 37°C.
  • Transforming nanosheets into nanocapsules via photoreactive molecular glue and photochemical crosslinking.
  • Loading nanocapsules with doxorubicin for targeted cancer cell treatment.

Main Results:

  • Successful formation of a tubulin nanosheet and its subsequent conversion into a stable nanocapsule.
  • Demonstrated selective response of the nanocapsule to GTP.
  • Induction of cancer cell death upon uptake of doxorubicin-loaded, crosslinked nanocapsules.

Conclusions:

  • The novel microtubule-based nanocapsule selectively responds to GTP, enabling targeted drug delivery.
  • This selective GTP response minimizes off-target effects in normal tissues, improving therapeutic potential.
  • The developed nanocapsules offer a promising platform for treating GTP-overexpressing cancers and RNA viral infections.

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