Tubulin-Based Nanotubes as Delivery Platform for Microtubule-Targeting Agents.
anticancer therapy
drug delivery
microtubule-targeting agents
nanomedicine
tubulin nanotubes
Journal
Advanced materials (Deerfield Beach, Fla.)
ISSN: 1521-4095
Titre abrégé: Adv Mater
Pays: Germany
ID NLM: 9885358
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
29
04
2020
revised:
27
05
2020
pubmed:
25
6
2020
medline:
11
6
2021
entrez:
25
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32579276
doi: 10.1002/adma.202002902
doi:
Substances chimiques
Antineoplastic Agents
0
Drug Carriers
0
Tubulin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2002902Subventions
Organisme : NRF
ID : 2018R1A3B1052661
Organisme : NRF
ID : 2018M3A9B5023527
Organisme : KAERI
Organisme : KUSTAR-KAIST Institute
Informations de copyright
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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