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Cancer-targeted and glutathione-responsive micellar carriers for controlled delivery of cabazitaxel

机译：癌症靶向和谷胱甘肽响应胶束载体，用于对Cabazitaxel的受控输送

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摘要

Novel type of multifunctional polymeric micelles (PMs) designated as HM-PMss/CTX micelles were developed in the present study for tumor-targeted and glutathione (GSH)-responsive delivery of cabazitaxel (CTX). The surface of the vehicles was modified with piloting molecules (HM-3 peptide), which targets alpha(v)beta(3) integrin overexpressed on cancer cells, and the micelle core was cross-linked by GSH-disintegrable disulfide linkages for controlled drug release. HM-PMss/CTX micelles were prepared using a mixture of two functionalized amphiphilic block copolymers and found to physically encapsulate CTX with excellent entrapment efficiency (93.94 +/- 4.19%), drug-loading capacity (8.39 +/- 2.28%), and a narrow size distribution. In vitro release profiles showed that CTX remained stably entrapped in the micelles in a release medium without GSH or with GSH of low concentration, while undergoing a rapid release in a highly reductive environment. Cellular uptake experiments showed that the conjugation of the targeting peptide, containing an arginine-glycine-aspartate sequence, enhanced the cellular uptake of HM-PMss/CTX micelles via alpha(v)beta(3) integrin-mediated endocytosis. In vitro cell viability measurements revealed that blank micelles were biocompatible, while HM-PMss/CTX micelles, owing to their tumor-targeting ability and GSH sensitivity, effectively inhibited the proliferation of MDA-MB-231 breast cancer cells. These results indicate that HM-PMss/CTX micelles could be a promising platform for future intelligent drug delivery in cancer therapy.
机译：作为HM-PMSS / CTX胶束指定为HM-PMS / CTX胶束的新型多官能聚合物胶束（PMS），用于Cabazitaxel（CTX）的肿瘤靶向和谷胱甘肽（GSH） - 夸张的递送。用试点分子（HM-3肽）改性载体的表面，其靶向α（v）β（3）整合蛋白在癌细胞上过表达，胶束核心通过GSH-崩解的二硫键与受控药物交联释放。使用两种官能化两亲嵌段共聚物的混合物制备HM-PMS / CTX胶束，并发现具有优异的夹带效率（93.94 +/- 4.19％），药物负载能力（8.39 +/- 2.28％），以及狭窄的分布。体外释放曲线显示CTX在没有GSH或GSH的释放培养基中稳定地夹在胶束中，或者具有低浓度的GSH，同时在高度还原环境中进行快速释放。蜂窝摄取实验表明，靶向肽的缀合，含有精氨酸 - 甘氨酸 - 天冬氨酸序列，通过α（v）β（3）整联蛋白介导的内吞作用增强了HM-PMS / CTX胶束的细胞吸收。体外细胞活力测量显示，由于其肿瘤靶向能力和GSH敏感性，HM-PMS / CTX胶束的坯料胶束是生物相容的，因此有效地抑制了MDA-MB-231乳腺癌细胞的增殖。这些结果表明，HM-PMS / CTX胶束可能是癌症治疗中未来智能药物递送的有希望的平台。

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  • 来源
    《Nanotechnology》 |2019年第5期|共14页
  • 作者

    Han Xiaoxiong; Gong Feirong; Chi Lili; Feng Caochuan; Sun Jing; Chen Yiyang; Liu Jianwen; Shen Yaling;

  • 作者单位

    East China Univ Sci &

    Technol Shanghai Collaborat Innovat Ctr Biomfg Technol State Key Lab Bioreactor Engn Shanghai 200237 Peoples R China;

    East China Univ Sci &

    Technol Sch Mat Sci &

    Engn Key Lab Ultrafine Mat Minist Educ Shanghai 200237 Peoples R China;

    Shandong Univ Tradit Chinese Med Dept Gastroenterol Affiliated Hosp Jinan 250011 Shandong Peoples R China;

    East China Univ Sci &

    Technol Shanghai Collaborat Innovat Ctr Biomfg Technol State Key Lab Bioreactor Engn Shanghai 200237 Peoples R China;

    East China Univ Sci &

    Technol Shanghai Collaborat Innovat Ctr Biomfg Technol State Key Lab Bioreactor Engn Shanghai 200237 Peoples R China;

    East China Univ Sci &

    Technol Sch Pharm State Key Lab Bioreactor Engn Shanghai Key Lab Chem Biol Shanghai 200237 Peoples R China;

    East China Univ Sci &

    Technol Sch Pharm State Key Lab Bioreactor Engn Shanghai Key Lab Chem Biol Shanghai 200237 Peoples R China;

    East China Univ Sci &

    Technol Shanghai Collaborat Innovat Ctr Biomfg Technol State Key Lab Bioreactor Engn Shanghai 200237 Peoples R China;

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  • 正文语种 eng
  • 中图分类 特种结构材料;
  • 关键词

    GSH-responsive; tumor-targeting peptide; cabazitaxel; polymeric micelles;

    机译：GSH响应;肿瘤靶向肽;Cabazitaxel;聚合物胶束;

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