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Tailor-made spider-eggcase-silk spheres for efficient lysosomal drug delivery

机译：用于高效溶酶体药物递送的量身定制的蜘蛛蛋壳丝球

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摘要

Spider silks are attractive biopolymers due to their excellent mechanical properties and biomimetic potential. To optimize the electrostatic interaction for lysosomal drug delivery, a spider-eggcase-silk protein was genetically engineered using 5x His Tag with a tailor-made isoelectric point of 4.8. By a facile HFIP-on-oil method, silk spheres were assembled as rapidly as 10 s. After the post-treatment of ethanol, silk spheres were determined with an improved compressive modulus by AFM indentation. Under incubation of silk spheres in a Doxorubicin solution, a maximum of 35% Loading and average of 30% loading efficiency were determined. In the cytotoxicity experiment, silk spheres exhibited intrinsic biocompatibility and showed good control of the loaded drug in the neutral PBS solution. Significantly, by 96 h, the accumulative drug release at pH 4.5 was approximately 4.5-fold higher than that at pH 7.4. By conducting the platelet adhesion and hemolysis assay, Doxorubicin-loaded silk spheres exhibited good hemocompatibility. To further demonstrate this release behavior, within 24 h, Doxorubicin-loaded silk spheres were efficiently delivered to lysosomes and then released the payload to the nuclei of Hela cells.
机译：由于其优异的机械性能和仿生势，蜘蛛丝网是有吸引力的生物聚合物。为了优化溶酶体药物递送的静电相互作用，蜘蛛蛋壳丝蛋白在其标签上使用5倍的标签进行遗传工程化，其测量的等电点为4.8。通过容易的氢化素内油方法，丝球作为10秒迅速地组装。在乙醇后处理后，通过AFM压痕用改善的压缩模量测定丝球。在多柔比蛋白溶液中孵育丝球中的孵育，确定最多35％的负荷和平均载入效率为30％。在细胞毒性实验中，丝球显示出内在的生物相容性，并良好地控制中性PBS溶液中的负载药物。显着地，通过96小时，pH 4.5的累积药物释放比pH7.4的高约4.5倍。通过进行血小板粘附和溶血测定，载荷型丝球的纯度呈现良好的血液相色性。为了进一步证明该释放行为，在24小时内，有效地将多柔比蛋白加载的丝球有效地递送至溶酶体，然后将有效载荷释放到HeLa细胞的细胞核中。

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  • 来源
    《RSC Advances》 |2018年第17期|共8页
  • 作者

    Chen Jianming; Hu Jinlian; Zuo Peijun; Su Xiaoqian; Liu Zhigao; Yang Mo;

  • 作者单位

    Hong Kong Polytech Univ Inst Text &

    Clothing Kowloon Hong Kong Peoples R China;

    Hong Kong Polytech Univ Inst Text &

    Clothing Kowloon Hong Kong Peoples R China;

    Hong Kong Univ Sci &

    Technol Nano &

    Adv Mat Inst Kowloon Hong Kong Peoples R China;

    Nanyang Technol Univ Sch Chem &

    Biomed Engn Singapore Singapore;

    Shenzhen PKU HKUST Med Ctr Shenzhen Guangdong Peoples R China;

    Hong Kong Polytech Univ Dept Biomed Engn Kowloon Hong Kong Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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