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Multifunctional Mesoporous Silica Nanoparticles for Cancer-Targeted and Controlled Drug Delivery

机译：多功能介孔二氧化硅纳米粒子的癌症靶向和控制药物输送。

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Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino-β-cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mes-opores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong /i-cyclodextrin/ada-mantane complexation. The non-cytotoxic nanoparticles containing the folate targeting units are efficiently trapped by folate-receptor-rich HeLa cancer cells through receptor-mediated endocytosis, while folate-receptor-poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β-cyclodextrin capping rings by cleaving the pre-installed disulfide bonds, further promoting the release of doxorubicin from the drug carriers. The high drug-delivery efficacy of the multifunctional nanoparticles is attributed to the co-operative effects of folate-mediated targeting and stimuli-triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.
机译：为了以靶向和受控方式将抗癌药物递送至特定癌细胞，开发了多功能介孔二氧化硅纳米颗粒。纳米颗粒表面被可裂解的二硫键桥接的氨基-β-环糊精环官能化，从而阻止了纳米颗粒介孔内的药物。在一端用金刚烷单元和在另一端用叶酸单元官能化的聚（乙二醇）聚合物通过强的i-环糊精/ ada-mantane络合固定在纳米粒子表面。富含叶酸受体的HeLa癌细胞通过受体介导的内吞作用有效地捕获了含有叶酸靶向单元的非细胞毒性纳米颗粒，而缺乏叶酸受体的人类胚胎肾脏293正常细胞在相同条件下对纳米颗粒的内吞作用低得多。癌细胞内吞的纳米颗粒可以通过酸性内体pH触发将负载的阿霉素释放到细胞中。纳米粒子从内体逃逸并进入癌细胞的细胞质后，细胞质中高浓度的谷胱甘肽可通过裂解预先安装的二硫键而导致β-环糊精封端环的去除，从而进一步促进β-环糊精的释放。阿霉素来自药物载体。多功能纳米颗粒的高药物传递功效归因于叶酸介导的靶向作用和刺激触发的药物释放的协同作用。能够以靶向和受控方式递送药物的本递送系统为下一代治疗剂提供了新颖的平台。

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  • 来源
    《Advanced Functional Materials》 |2012年第24期|5144-5156|共13页
  • 作者

    Quan Zhang; Fang Liu; Kim True Nguyen; Xing Ma; Xiaojun Wang; Bengang Xing; Yanli Zhao;

  • 作者单位

    Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link, Singapore 637371;

    Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link, Singapore 637371;

    Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link, Singapore 637371;

    School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue, Singapore 639798;

    Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link, Singapore 637371;

    Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link, Singapore 637371;

    Division of Chemistry and Biological Chemistry School of Physical and Mathematical Sciences Nanyang Technological University 21 Nanyang Link, Singapore 637371,School of Materials Science and Engineering Nanyang Technological University 50 Nanyang Avenue, Singapore 639798;

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