title: Tumor detection using magnetosome nanoparticles functionalized with a newly screened EGFR/HER2 targeting peptide.
abstract: A novel peptide (P75) targeting EGFR and HER2 is successfully screened from a one-bead-one-compound (OBOC) library containing approximately 2 × 105peptides 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.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; Sino-Danish Center for Education and Research, Beijing 101408, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhichu
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratories for Agro-biotechnology and College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Lai
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China. Electronic address: huzy@nanoctr.cn.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratories for Agro-biotechnology and College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: tianhome@cau.edu.cn.
authors.forename: Jiesheng
authors.initials: J
authors.lastname: Tian
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: linggengling@163.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Geng
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China; CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China. Electronic address: fangqj@nanoctr.cn.
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: Fang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D055944:Magnetosomes / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015336:Molecular Probe Techniques; D015335:Molecular Probes; D058726:Nanoconjugates / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000493:pharmacokinetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D066246:ErbB Receptors; D015335:Molecular Probes; D058726:Nanoconjugates; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; EGFR/HER2 targeting peptide; Magnetosome; Molecular dynamics (MD) simulation; Targeted MRI