Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles,Particle & Particle Systems Characterization

当前位置： X-MOL 学术 › Part. Part. Syst. Charact. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles
Particle & Particle Systems Characterization ( IF 2.7 ) Pub Date : 2020-05-25 , DOI: 10.1002/ppsc.202000040
Naroa Serna _{1,

2,

3} , Olivia Cano‐Garrido _{1,

2,

3} , Laura Sánchez‐García _{1,

2,

3} , Mireia Pesarrodona _{1,

2,

3} , Ugutz Unzueta _{3,

4} , Alejandro Sánchez‐Chardi _{5,

6} , Ramon Mangues _{3,

4} , Esther Vázquez _{1,

2,

3} , Antonio Villaverde _{1,

2,

3}

Affiliation

Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self‐assembling multimeric nanoparticles. Incorporated in modular constructs including a C‐terminal polyhistidine tag and an N‐terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4⁺ tumor cells in a CXCR4‐dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor‐targeted nanomaterials for selective theragnostic applications in CXCR4⁺ cancers.

中文翻译：

将蛋白毒液工程化为自组装的靶向CXCR4的细胞毒纳米颗粒

蛋白质毒液是有效的细胞毒性分子，当方便地靶向肿瘤标记物时，它们可以被用作有前途的抗癌药物。在这里，我们探索了当以GFP融合形式作为自组装多聚体纳米颗粒进行工程改造时，与结构无关的蜂毒肽，gomesin和CLIP71是否具有功能活性。这些毒液被掺入模块化构建体中，包括C端多组氨酸标签和细胞因子受体CXCR4的N端肽配体（在20多个人类肿瘤中过表达），在重组细菌中可以很好地产生这些毒液，其蛋白水解稳定的规则纳米颗粒范围在12至12之间。 35纳米这些材料具有强荧光性，可以选择性地渗透，标记和杀死CXCR4 ⁺CXCR4依赖性肿瘤细胞。所获得的数据通过精确配制为靶向肿瘤的纳米材料，用于CXCR4 ⁺癌症的选择性血管吻合术，支持了重组毒液作为有前景的药物的概念。

更新日期：2020-05-25

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11