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首页> 外文期刊>International Journal of Biological Macromolecules: Structure, Function and Interactions >Tumor-targeting and pH-responsive nanoparticles from hyaluronic acid for the enhanced delivery of doxorubicin
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Tumor-targeting and pH-responsive nanoparticles from hyaluronic acid for the enhanced delivery of doxorubicin

机译：透明质酸肿瘤靶向和pH-响应纳米粒子，用于增强多柔比星的递送

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摘要

In this study, intracellular pH-responsive nanoparticles (NPs) of hyaluronic acid-hydrazone linkage-doxorubicin (HA-hyd-DOX) were designed and prepared for acid-triggered release of doxorubicin through a hydrazone linkage. A series of amphiphilic polymeric prodrugs were obtained, which can be self-assembled in aqueous media, the formed NPs exhibited a spherical core-shell type and the uniform size was ranging from 167 to 220 nm. Moreover, the HA-hyd-DOX NPs exhibited a good stability in vitro and the drug release profiles showed that the DOX release was obviously mediated by pH gradient. Additionally, the cell counting assay kit-8 (CCK-8) demonstrated that the drug delivery system in this study performed a lower cytotoxicity on normal cells (Mouse fibroblast cells, L929) and higher inhibition ratio on tumor cells (Human cervical cancer cells, HeLa) in response to drug release with the intracellular pH environment. Furthermore, confocal laser scanning microscopy (CLSM) images and flow cytometric profiles of HeLa cells showed an efficiently cellular uptake due to the receptor-mediated affinity of CD44 for HA with high specificity. These results suggest that this pH dependent drug delivery system based on HA will provide insights into the design of potential prodrugs for the cancer therapy. (C) 2018 Elsevier B.V. All rights reserved.
机译：在该研究中，设计并制备了通过腙键合的酸性释放多柔比星的细胞内pH-响应纳米粒子（NPS）。得到一系列两亲性聚合物前药，其可以在水性介质中自组装，形成的NPS表现出球形芯壳类型，均匀的尺寸范围为167-220nm。此外，HA-HYD-DOX NPS在体外表现出良好的稳定性，药物释放曲线显示DOX释放明显是通过pH梯度介导的。另外，细胞计数测定试剂盒-8（CCK-8）证明该研究中的药物递送系统对正常细胞（小鼠成纤维细胞，L929）和肿瘤细胞（人宫颈癌细胞的抑制率较高）进行下细胞毒性。 Hela）响应药物释放与细胞内pH环境。此外，引起的共聚焦激光扫描显微镜（CLSM）图像和流式细胞术谱的图像和流式细胞术谱表明，由于CD44具有高特异性的CD44对HA的受体介导的亲和力而有效的摄影。这些结果表明，基于HA的pH依赖药物输送系统将为癌症治疗的潜在前药设计提供见解。 （c）2018年elestvier b.v.保留所有权利。

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