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首页> 外文期刊>Scientific reports. >Targeted delivery system for cancer cells consist of multiple ligands conjugated genetically modified CCMV capsid on doxorubicin GNPs complex
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Targeted delivery system for cancer cells consist of multiple ligands conjugated genetically modified CCMV capsid on doxorubicin GNPs complex

机译:针对癌细胞的靶向递送系统由多个配体缀合的遗传修饰的CCMV衣壳组成,在多柔比星GNPS复合物上

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Targeted nano-delivery vehicles were developed from genetically modified Cowpea chlorotic mottle virus (CCMV) capsid by ligands bioconjugation for efficient drug delivery in cancer cells. RNA binding (N 1-25aa) and β-hexamer forming (N 27-41aa) domain of capsid was selectively deleted by genetic engineering to achieve the efficient in vitro assembly without natural cargo. Two variants of capsids were generated by truncating 41 and 26 amino acid from N terminus (NΔ41 and NΔ26) designated as F1 and F2 respectively. These capsid were optimally self-assembled in 1:2 molar ratio (F1:F2) to form a monodisperse nano-scaffold of size 28?nm along with chemically conjugated modalities for visualization (fluorescent dye), targeting (folic acid, FA) and anticancer drug (doxorubicin). The cavity of the nano-scaffold was packed with doxorubicin conjugated gold nanoparticles (10?nm) to enhance the stability, drug loading and sustained release of drug. The chimeric system was stable at pH range of 4-8. This chimeric nano-scaffold system showed highly specific receptor mediated internalization (targeting) and ~300% more cytotoxicity (with respect to FA(-) delivery system) to folate receptor positive Michigan Cancer Foundation-7 (MCF7) cell lines. The present system may offer a programmable nano-scaffold based platform for developing chemotherapeutics for cancer.
机译:通过配体生物缀合物从遗传修饰的豇豆氯化斑块病毒(CCMV)衣壳中,通过配体生物杂交来开发目标纳米递送载体,以便在癌细胞中有效药物递送。通过基因工程选择性地删除衣壳的RNA结合(N 1-25AA)和β-六烷基形成(N 27-41AA)结构域,以实现没有天然货物的有效的体外组装。通过分别指定为F1和F2的N末端(Nδ41和Nδ26)截断41和26个氨基酸来产生两个衣壳的两种变体。这些衣壳在1:2摩尔比(F1:F2)中最佳地自组装,形成大小28Ω·Nm的单分散纳米支架以及化学共轭方式,用于可视化(荧光染料),靶向(叶酸,FA)和抗癌药物(多柔比星)。纳米支架的腔用多柔比星共轭金纳米颗粒(10·NM)填充,以增强药物的稳定性,药物载荷和持续释放。嵌合体系在4-8的pH范围内稳定。这种嵌合纳米支架系统显示出高度特异性受体介导的内化(靶向)和〜300%的细胞毒性(关于FA( - )输送系统),对叶酸受体阳性密歇根癌癌基础-7(MCF7)细胞系。本系统可以提供基于可编程纳米支架的基于平台,用于开发癌症的化学治疗剂。

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