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Tubulin‐Based Nanotubes as Delivery Platform for Microtubule‐Targeting Agents
Author(s) -
Kim Jinjoo,
Lee Juncheol,
Lee Jimin,
Keum Hyeongseop,
Kim Yumi,
Kim Yujin,
Yu Byeongjun,
Lee Sang Yeop,
Tanaka Junichi,
Jon Sangyong,
Choi Myung Chul
Publication year - 2020
Publication title -
advanced materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 10.707
H-Index - 527
eISSN - 1521-4095
pISSN - 0935-9648
DOI - 10.1002/adma.202002902
Subject(s) - tubulin , microtubule , in vivo , materials science , drug , drug delivery , in vitro , nanotechnology , biophysics , cancer research , microbiology and biotechnology , chemistry , pharmacology , biology , biochemistry
Abstract 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.