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Dendronized hyaluronic acid-docetaxel conjugate as a stimuli-responsive nano-agent for breast cancer therapy.

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机构： [a]Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, Department of Breast Surgery, Clinical Research Center for Breast, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China [b]Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China [c]College of Preclinical Medicine, Southwest Medical University, Luzhou 646000, China [d]Amgen Bioprocessing Centre, Keck Graduate Institute, CA 91711, USA

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To achieve target delivery of anti-tumor drugs with great biocompatibility into tumor tissues, a stimuli-responsive dendronized hyaluronic acid (HA)-docetaxel conjugate (HA-DTX-Dendron, HADD) was designed and prepared. The incorporation of HA in HADD improved the delivery of DTX to tumor cells with rich CD44 receptors. Enhanced biocompatibility and therapeutic outcomes were achieved using glyodendrons-modified HA and tumor microenvironment-responsive linkers in HADD. The glycodendron was connected with HA via GSH-responsive disulfide bonds, and the drug DTX was linked to the carrier via a cathepsin B-responsive tetrapeptide GFLG. This design resulted in self-assembly nanostructures for facilitating uptake of HADD by tumor cells and rapid release of DTX to exert its therapeutic effect. Compared to free DTX, HADD showed much higher tumor growth inhibition in the MDA-MB-231 tumor-bearing mice model (up to 99.71%), and no toxicity was observed. Therefore, HADD could be employed as an efficacious nano-agent for treating triple negative breast cancer (TNBC).Copyright © 2021 Elsevier Ltd. All rights reserved.

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出版当年[2021]版：

大类 | 1 区

化学

小类 | 1 区应用化学 1 区有机化学 1 区高分子科学

最新[2023]版：

大类 | 1 区

化学

小类 | 1 区应用化学 1 区有机化学 1 区高分子科学

第一作者：

第一作者机构： [a]Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, Department of Breast Surgery, Clinical Research Center for Breast, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China

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通讯作者：

通讯机构： [a]Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, Department of Breast Surgery, Clinical Research Center for Breast, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China [b]Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China [*1]Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China

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