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Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2017-09-25 , DOI: 10.1002/adhm.201700596
Francesca Biscaglia 1 , Senthilkumar Rajendran 2 , Paolo Conflitti 3 , Clara Benna 2 , Roberta Sommaggio 2 , Lucio Litti 1 , Simone Mocellin 2, 4 , Gianfranco Bocchinfuso 3 , Antonio Rosato 2, 4 , Antonio Palleschi 3 , Donato Nitti 2 , Marina Gobbo 1 , Moreno Meneghetti 1
Affiliation  

Plasmonic nanostructures show important properties for biotechnological applications, but they have to be guided on the target for exploiting their potentialities. Antibodies are the natural molecules for targeting. However, their possible adverse immunogenic activity and their cost have suggested finding other valid substitutes. Small molecules like peptides can be an alternative source of targeting agents, even if, as single molecules, their binding affinity is usually not very good. GE11 is a small dodecapeptide with specific binding to the epidermal growth factor receptor (EGFR) and low immunogenicity. The present work shows that thousands of polyethylene glycol (PEG) chains modified with lysines and functionalized with GE11 on clusters of naked gold nanoparticles, obtained by laser ablation in water, achieves a better targeting activity than that recorded with nanoparticles decorated with the specific anti‐EGFR antibody Cetuximab (C225). The insertion of the cationic spacer between the polymeric part of the ligand and the targeting peptide allows for a proper presentation of GE11 on the surface of the nanosystems. Surface enhanced resonance Raman scattering signals of the plasmonic gold nanoparticles are used for quantifying the targeting activity. Molecular dynamic calculations suggest that subtle differences in the exposition of the peptide on the PEG sea are important for the targeting activity.

中文翻译:

工程GE11肽增强了电浆纳米结构的EGFR靶向活性

等离子体等离子纳米结构在生物技术应用中显示出重要的性能,但是必须在目标上加以指导,以发挥其潜力。抗体是用于靶向的天然分子。但是,它们可能的不利的免疫原性活性和成本提示寻找其他有效的替代品。小分子(如肽)可以作为靶向剂的替代来源,即使它们作为单分子的结合亲和力通常不是很好。GE11是小的十二肽,具有与表皮生长因子受体(EGFR)的特异性结合且免疫原性低。目前的工作表明,在水中通过激光烧蚀获得的几千个用赖氨酸修饰并用GE11官能化的聚乙二醇(PEG)链,在裸金纳米颗粒的簇上,与使用特异性抗EGFR抗体西妥昔单抗(C225)修饰的纳米颗粒所记录的靶向活性相比,它具有更好的靶向活性。阳离子间隔基在配体的聚合物部分和靶向肽之间的插入允许GE11在纳米系统表面上正确呈现。等离子体金纳米颗粒的表面增强共振拉曼散射信号用于定量靶向活性。分子动力学计算表明,肽在PEG海洋上的微妙差异对于靶向活性很重要。阳离子间隔基在配体的聚合物部分和靶向肽之间的插入允许GE11在纳米系统表面上正确呈现。等离子体金纳米颗粒的表面增强共振拉曼散射信号用于定量靶向活性。分子动力学计算表明,肽在PEG海洋上的微妙差异对于靶向活性很重要。阳离子间隔基在配体的聚合物部分和靶向肽之间的插入允许GE11在纳米系统表面上正确呈现。等离子体金纳米颗粒的表面增强共振拉曼散射信号用于定量靶向活性。分子动力学计算表明,肽在PEG海洋上的微妙差异对于靶向活性很重要。
更新日期:2017-09-25
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