title: Intracellular Self-Assembly of Taxol Nanoparticles for Overcoming Multidrug Resistance.
abstract: Multidrug resistance (MDR) remains the biggest challenge in treating cancers. Herein we propose the intracellular self-assembly of nanodrugs as a new strategy for overcoming MDR. By employing a biocompatible condensation reaction, we rationally designed a taxol derivative Ac-Arg-Val-Arg-Arg-Cys(StBu)-Lys(taxol)-2-cyanobenzothiazole (CBT-Taxol) which could be subjected to furin-controlled condensation and self-assembly of taxol nanoparticles (Taxol-NPs). In vitro and in vivo studies indicated that, compared with taxol, CBT-Taxol showed a 4.5-fold or 1.5-fold increase in anti-MDR effects, respectively, on taxol-resistant HCT 116 cancer cells or tumors without being toxic to the cells or the mice. Our results demonstrate that structuring protease-susceptible agents and assembling them intracellularly into nanodrugs could be a new optimal strategy for overcoming MDR.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China).
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn.
authors.forename: Zhanling
authors.initials: Z
authors.lastname: Ding
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn.
authors.forename: Linna
authors.initials: L
authors.lastname: An
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027 (China). hzhang22@ustc.edu.cn.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 (China) http://lianglab.ustc.edu.cn. gliang@ustc.edu.cn.
authors.forename: Gaolin
authors.initials: G
authors.lastname: Liang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D052160:Benzothiazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D045325:HCT116 Cells; D006801:Humans; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D009570:Nitriles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: C578355:2-cyanobenzothiazole; D000972:Antineoplastic Agents, Phytogenic; D052160:Benzothiazoles; D009570:Nitriles; D017239:Paclitaxel
keywords: furin; multidrug resistance; nanoparticles; self-assembly; taxol