Chen Jianming, Hu Jinlian, Zuo Peijun, Su Xiaoqian, Liu Zhigao, Yang Mo
Institute of Textiles and Clothing, The Hong Kong Polytechnic University Hung Hom Kowloon Hong Kong
Nano and Advanced Materials Institute, The Hong Kong University of Science and Technology Clear Water Bay Kowloon Hong Kong.
RSC Adv. 2018 Mar 6;8(17):9394-9401. doi: 10.1039/c8ra00232k. eCollection 2018 Feb 28.
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 5× 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.
蜘蛛丝因其出色的机械性能和仿生潜力而成为具有吸引力的生物聚合物。为了优化用于溶酶体药物递送的静电相互作用，利用具有4.8的定制等电点的5×His标签对蜘蛛卵囊丝蛋白进行了基因工程改造。通过简便的油上HFIP方法，可在10秒内快速组装丝球。经过乙醇后处理，通过原子力显微镜压痕测定丝球具有提高的压缩模量。在丝球于阿霉素溶液中孵育后，测定的最大负载量为35%，平均负载效率为30%。在细胞毒性实验中，丝球表现出内在的生物相容性，并且在中性PBS溶液中对负载药物具有良好的控制。值得注意的是，到96小时时，pH 4.5下的累积药物释放量比pH 7.4下的约高4.5倍。通过进行血小板粘附和溶血试验，负载阿霉素的丝球表现出良好的血液相容性。为了进一步证明这种释放行为，在24小时内，负载阿霉素的丝球被有效地递送至溶酶体，然后将有效载荷释放到HeLa细胞核中。
