Tubulin-Based Nanotubes as Delivery Platform for Microtubule-Targeting Agents

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Tubulin-based nanotubes (TNTs) to deliver microtubule-targeting agents (MTAs) for clinical oncology are reported. Three MTAs, docetaxel (DTX), laulimalide (LMD), and monomethyl auristatin E (MMAE), which attach to different binding sites in a tubulin, are loaded onto TNTs and cause structural changes in them, including shape anisotropy and tubulin layering. This drug-driven carrier transformation leads to changes in the drug-loading efficiency and stability characteristics of the carrier. TNTs coloaded with DTX and LMD efficiently deliver dual drug cargoes to cellular tubulins by the endolysosomal pathway, and results in synergistic anticancer and antiangiogenic action of the drugs in vitro. In in vivo tests, TNTs loaded with a microtubule-destabilizing agent MMAE suppress the growth of tumors with much higher efficacy than free MMAE did. This work suggests a new concept of using a drug's target protein as a carrier. The findings demonstrate that the TNTs developed here can be used universally as a delivery platform for many MTAs.
Publisher
WILEY-V C H VERLAG GMBH
Issue Date
2020-06
Language
English
Article Type
Article
Citation

ADVANCED MATERIALS, v.32, no.33

ISSN
0935-9648
DOI
10.1002/adma.202002902
URI
http://hdl.handle.net/10203/282021
Appears in Collection
BS-Journal Papers(저널논문)BiS-Journal Papers(저널논문)
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