Tumor detection using magnetosome nanoparticles functionalized with a newly screened EGFR/HER2 targeting peptide

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• 作者：Zhichu Xiang^a ; ^b ; ^c ; ^d ; Xiaoliang Yang^a ; ^b ; ^d ; Junjie Xu^f ; Wenjia Lai^a ; ^b ; Zihua Wang^a ; ^b ; ^d ; Zhiyuan Hu^a ; ^b ; ^{huzy@nanoctr.cn} ; Jiesheng Tian^f ; ^{tianhome@cau.edu.cn} ; Lingling Geng^a ; ^e ; ^{linggengling@163.com} ; Qiaojun Fang^a ; ^b ; ^{fangqj@nanoctr.cn}
• 关键词：EGFR/HER2 targeting peptide ; Molecular dynamics (MD) simulation ; Magnetosome ; Targeted MRI ; Breast cancer
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：115
• 期：Complete
• 页码：53-64
• 全文大小：3568 K
• 卷排序：115

文摘

A novel peptide (P75) targeting EGFR and HER2 is successfully screened from a one-bead-one-compound (OBOC) library containing approximately 2 × 105 peptides built with the aid of computational simulation. In vitro and in vivo analyses show that P75 binds to human epithelial growth factor receptor (EGFR) with nanomolar affinity and to epithelial growth factor receptor-2 (HER2) with a lower affinity but comparable to other reported peptides. The peptide is used to modify the surface of magnetosome nanoparticles (NPs) for targeted magnetic resonance imaging (MRI). In vitro and in vivo fluorescence imaging results suggest peptide P75 modified magnetosomes (Mag-P75) specifically bind to MDA-MB-468 and SKBR3 cells as well as xenograft tumors with surprisingly low accumulation in other organs including liver and kidney. In vivo T2-weighted MR imaging studies of the xenograft tumors from SKBR3 and MDA-MB-468 cells show obviously negative contrast enhancement. The high affinity and specificity of P75 to EGFR and HER2 positive tumors, together with the success of peptide functionalized magnetosome NPs for targeted MRI demonstrate the potential of this peptide being used in the EGFR and HER2 positive tumors diagnosis and therapy.