title: Paclitaxel dimers assembling nanomedicines for treatment of cervix carcinoma.
abstract: Poor water solubility and adverse side effects pose a challenge for clinical application of paclitaxel (PTX). In this work, a series of PTX dimers are synthesized by coupling two PTX molecules with dicarboxylic acids. As-synthesized PTX dimers form stable nanoparticles in aqueous solution without using any surfactants or adjuvants, and the solubility of PTX in water increases by 2500-fold compared to that of free PTX. These nanoparticles with high content of PTX are internalized by cancer cells and exhibit comparable cytotoxicity with Taxol. Furthermore, when the PTX dimers are incorporated into methoxypoly(ethylene glycol)2K-block-poly(d, l-lactide)2K(PEG-PDLLA) micelles, the loading content of PTX dimers is as high as 85wt%. The formed nanoparticles possess the high stability in biological conditions. Both in vitro and in vivo experiments show that these (PTX dimer)/PEG-PDLLA formulations possess effective cellular uptake and potent cytotoxicity, and exhibit reduced systemic toxicity and enhanced antitumor efficacy towards human cervical tumor. We believe these PTX dimers-based nanoparticles would be an alternative formulation for PTX, and such drug dimer assembling behaviors could be extended to other therapeutic agents.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, PR China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, PR China.
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, PR China. Electronic address: xiez@ciac.ac.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun, Jilin 130022, PR China.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002584:Cervix Uteri / Q000187:drug effects* / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D019281:Dimerization; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004355:Drug Stability; D005260:Female; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008823:Micelles; D050997:Nanomedicine / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Dimer; Nanomedicine; Paclitaxel; Self-assembly