Genetically-engineered protein prodrug-like nanoconjugates for tumor-targeting biomimetic delivery via a SHEATH strategy
文献类型：期刊论文
| 作者 | Chang, Ya1; Yao, Shuo1; Chen, Yifang1; Huang, Jingjing1; Wu, Aihua1; Zhang, Meng1; Xu, Fan1; Li, Feng2; Huang, Yongzhuo1
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| 刊名 | Nanoscale
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| 出版日期 | 2018-12-17 |
| ISSN号 | 2040-3372 |
| DOI | 10.1039/c8nr08951e |
| 文献子类 | Article |
| 英文摘要 | The delivery issue is a major hurdle against drug development and the clinical application of the cytoplasmic active proteins (e.g., ribosome-inactivating proteins, RIPs). As a case in point, trichosanthin (TCS) has a very high cytoplasmic activity of killing cancer cells, but the translation is hampered by its unfavorable nature, such as the short half-life, poor tumor targeting and cell permeation. To address this issue, a novel delivery method called a smart hitchhike via endogenous albumin-trichosanthin hinge (SHEATH) system was developed by the genetic fusion of an albumin-binding domain (ABD) and a legumain-substrate peptide to TCS. The SHEATH system is characterized by the feature of smart hitchhike by binding to serum albumin via its ABD domain, and the two proteins (i.e., TCS and albumin) thus form a prodrug-like noncovalent nanoconjugate. The TCS could detach from the albumin carrier by responding to the protease legumain cleavage of the substrate peptide at the tumor site. Such a system can take advantage of the albumin-mediated biomimetic delivery to the tumor via the nutrient transporter pathway of albumin-binding proteins (e.g., SPARC). The antitumor effects were evaluated in orthotopic breast cancer animal models and showed remarkably improved antitumor effects. Our work provides a useful protocol for improving the druggability of such a class of protein toxins for targeted cancer therapy by an endogenous albumin-hitchhike strategy. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266723]  |
| 专题 | 新药研究国家重点实验室 药物制剂研究中心 |
| 通讯作者 | Chang, Ya; Yao, Shuo; Chen, Yifang; Huang, Jingjing; Wu, Aihua; Zhang, Meng; Xu, Fan; Huang, Yongzhuo |
| 作者单位 | 1.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China; 2.Auburn University Harrison School of Pharmacy, Auburn, AL 36849, USA |
| 推荐引用方式 GB/T 7714 | Chang, Ya,Yao, Shuo,Chen, Yifang,et al. Genetically-engineered protein prodrug-like nanoconjugates for tumor-targeting biomimetic delivery via a SHEATH strategy[J]. Nanoscale,2018. |
| APA | Chang, Ya.,Yao, Shuo.,Chen, Yifang.,Huang, Jingjing.,Wu, Aihua.,...&Huang, Yongzhuo.(2018).Genetically-engineered protein prodrug-like nanoconjugates for tumor-targeting biomimetic delivery via a SHEATH strategy.Nanoscale. |
| MLA | Chang, Ya,et al."Genetically-engineered protein prodrug-like nanoconjugates for tumor-targeting biomimetic delivery via a SHEATH strategy".Nanoscale (2018). |
入库方式： OAI收割
来源：上海药物研究所
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