한빛사 논문
Jinjoo Kima, Juncheol Leeb, Jimin Leeb, Hyeongseop Keuma, Yumi Kimb, Yujin Kima, Byeongjun Yua, Sang Yeop Leeb, Junichi Tanakac, Sangyong Jona,* and Myung Chul Choib,*
aDepartment of Biological Sciences, Center for Precision Bio-Nanomedicine, Korea Advanced Institute of Science and Technology (KAIST), Daehak-ro 34141, Daejeon, Korea
bDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daehak-ro 34141, Daejeon, Korea
cDepartment of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
*To whom correspondence should be addressed.
J.K. and J.L. contributed equally to this work
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.
Keywords : anticancer therapy, drug delivery, microtubule-targeting agents, nanomedicine, tubulin nanotubes
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