Tubulin-Based Nanotubes as Delivery Platform for Microtubule-Targeting Agents |
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Authors: | Jinjoo Kim Juncheol Lee Jimin Lee Hyeongseop Keum Yumi Kim Yujin Kim Byeongjun Yu Sang Yeop Lee Junichi Tanaka Sangyong Jon Myung Chul Choi |
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Affiliation: | 1. Department of Biological Sciences, Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141 Korea;2. Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Daejeon, 34141 Korea;3. Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa, 903-0213 Japan |
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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. |
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Keywords: | anticancer therapy drug delivery microtubule-targeting agents nanomedicine tubulin nanotubes |
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