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Folate-conjugated dually responsive micelles for targeted anticancer drug delivery

机译：针对靶向抗癌药物递送的叶酸缀合的双重响应胶束

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摘要

Phenylboronic acid and folate grafted chitosan hydrochloride (FHCSPBA) was synthesized and confirmed by FTIR and H-1 NMR. Glucose and pH dually responsive micelles were obtained through self-assembly of the amphiphilic polymers. The prepared FHCSPBA micelles displayed good biocompatibility and sustained drug release of the model drug doxorubicin hydrochloride (DOX). The cumulative drug release from the polymeric micelles showed obvious pH and glucose dependence and was accelerated by slightly decreasing the medium pH or increasing the glucose concentration. In vitro antitumor efficiency was evaluated by incubating the DOX loaded micelles with 4T1 breast cancer cells, and the results showed that folate-targeted micelles had higher antitumor activity than the non-targeted ones. Cellular uptake demonstrated by confocal microscopy indicated that free DOX was internalized in the nuclei of 4T1 cells, while the DOX loaded micelles were internalized in the cytoplasm. The cellular uptake of the micelles was enhanced by folate, with stronger fluorescence intensity in the cytoplasm, due to active FR-mediated endocytosis. These folate-conjugated glucose and pH dually responsive micelles may be a potential antitumor drug delivery system for cancer chemotherapy.
机译：通过FTIR和H-1 NMR合成并确认苯基硼酸和叶酸接枝壳聚糖（FHCSPBA）。通过两亲聚合物的自组装获得葡萄糖和pH双重响应胶束。制备的FHCSPBA胶束显示出良好的生物相容性和持续的药物释放药物Doxorubicin盐酸盐（DOX）。来自聚合物胶束的累积药物释放显示出明显的pH和葡萄糖依赖性，并通过稍微减少培养基或增加葡萄糖浓度来加速。通过将DOX装载的胶束与4T1乳腺癌细胞一起孵育，评价体外抗肿瘤效率，结果表明，叶酸纤维素的抗肿瘤活性高于非靶向胶束。共聚焦显微镜证明的细胞摄取表明，在4T1细胞的核中，自由DOX内化，而DOX负载胶束在细胞质中内化。由于活性FR介导的内吞作用，细胞质中具有较强的荧光强度，叶片增强了胶束的细胞吸收。这些叶酸缀合的葡萄糖和pH值响应胶束可以是癌症化疗的潜在抗肿瘤药物递送系统。

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  • 来源
    《RSC Advances》 |2016年第42期|共10页
  • 作者

    Zhao Lingling; Zhang Yajuan; Shao Jia; Liang Hongze; Na Haining; Zhu Jin;

  • 作者单位

    Ningbo Univ Fac Mat Sci &

    Chem Engn Ningbo 315211 Zhejiang Peoples R China;

    Ningbo Univ Fac Mat Sci &

    Chem Engn Ningbo 315211 Zhejiang Peoples R China;

    Ningbo Univ Fac Mat Sci &

    Chem Engn Ningbo 315211 Zhejiang Peoples R China;

    Ningbo Univ Fac Mat Sci &

    Chem Engn Ningbo 315211 Zhejiang Peoples R China;

    Chinese Acad Sci Ningbo Inst Mat Technol &

    Engn Ningbo Key Lab Polymer Mat Ningbo 315201 Zhejiang Peoples R China;

    Chinese Acad Sci Ningbo Inst Mat Technol &

    Engn Ningbo Key Lab Polymer Mat Ningbo 315201 Zhejiang Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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