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PH-triggered intracellular release from actively targeting polymer micelles

机译：从主动靶向聚合物胶束的pH-触发的细胞内释放

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摘要

Chemotherapy is widely applied to treat cancer patients but its application is limited due to the systemic toxicity and low efficacy. Nanocarrier system, which is capable of delivering their toxic cargos specifically into cancer cells and then greatly overcomes these disadvantages, has drawn a broad attention. Here we developed a drug-conjugated micelle for a better drug delivery in which folic acid was attached to the DOX-conjugated poly(ethylene glycol)-poly(ε-caprolactone) to target tumor; DOX was further connected with a hydrazone linker (FA-hyd) for a pH-triggered drug release. Comparing to other DOX-conjugated micelles either linked with carbamate (FA-cbm) or lacking FA(m-hyd), the developed FA-hyd demonstrated excellent biocompatibility; When analyzed with Alamar blue assays, flow cytometry and confocal laser scanning microscopy (CLSM), the pH-sensitive FA-functionalized DOX-conjugated micelles presented much better efficiency of cellular uptake and higher cytotoxicity to tumor cells. In vivo pharmacokinetics and biodistribution studies indicated that FA-hyd micelles significantly prolonged the blood circulation time of drug and enriched drug into the tumors rather than normal tissues. In vivo antitumor activity demonstrated that FA-hyd micelles had the highest safety to body and the best therapeutic efficacy to tumors. Therefore, this drug delivery system is deemed as a potential nanocarrier for cancer therapy.
机译：化疗广泛应用于治疗癌症患者，但由于系统性毒性和低疗效，其应用受到限制。纳米载波系统，能够专门将其有毒的尸体递送到癌细胞，然后大大克服这些缺点，引起了广泛的关注。在这里，我们开发了一种药物缀合的胶束，用于更好的药物递送，其中将叶酸连接到DOX缀合的聚（乙二醇） - 聚（ε-己内酯）中靶向肿瘤; DOX与腙接头（FA-HYD）相连，用于pH-触发的药物释放。与其他DOX缀合的胶束相比，与氨基甲酸酯（FA-CBM）连接或缺乏FA（M-HYD），发达的FA-HYD展示了优异的生物相容性;当用Alamar蓝色测定分析，流式细胞术和共焦激光扫描显微镜（CLSM）时，pH敏感的FA官能化DOX缀合的胶束呈现出细胞摄取和更高细胞毒性的更好效率与肿瘤细胞。体内药代动力学和生物分布研究表明，FA-HYD胶束显着延长了药物的血液循环时间，并将药物富集到肿瘤中而不是正常组织。体内抗肿瘤活性证明了FA-HYD胶束对身体的最高安全性和对肿瘤的最佳治疗效果。因此，该药物递送系统被认为是癌症治疗的潜在纳米载体。

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  • 来源
    《Biomaterials》 |2013年第18期|共11页
  • 作者

    GuoX.; ShiC.; WangJ.; DiS.; ZhouS.;

  • 作者单位

    Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials;

    School of Life Science and Engineering Southwest Jiaotong University Chengdu 610031 China;

    Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials;

    Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials;

    Key Laboratory of Advanced Technologies of Materials Ministry of Education School of Materials;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物医学工程;
  • 关键词

    Drug delivery; Nanotechnology; PH-sensitive; Polymeric micelle; Tumor targeting;

    机译：药物递送;纳米技术;pH敏感;聚合物胶束;肿瘤靶向;

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