Abstract |
Based on the discordance of human epidermal growth factor receptor-2 (HER2) expression between primary and metastatic/recurrent breast cancer, HER2 molecular imaging, which had potential to systemically assess and dynamically monitor HER2 expression, might improve the selection of patients for anti-HER2 therapy. In this study, designed ankyrin repeat protein ( DARPin) G3, a novel binding protein with picomolar affinity for HER2, was used and multifunctional superparamagnetic nanoparticles modified with fluorescein-5-maleimide-labeled DARPin G3 (SPIO-G3-5MF) were developed for HER2 imaging. Our results showed that SPIO-G3-5MF nanoparticles, which possessed uniform size of about 100 nm, favorable dispersity and low cytotoxicity, could selectively bind to HER2-positive breast cancer cells even in the presence of trastuzumab. Biodistribution assay demonstrated that abundant accumulation and long retention of SPIO-G3-5MF were observed in HER2-positive transplantation breast tumors although a portion of SPIO-G3-5MF nanoparticles were unavoidably captured by liver and spleen. Further MR imaging revealed that SPIO-G3-5MF could selectively image HER2-positive transplantation breast tumors, yielding remarkable T2 signal reduction (50.33 ± 2.90% at 6 h and 47.29 ± 9.36% at 24 h). Our study suggested that SPIO-G3-5MF might be a promising MR molecular probe for diagnosing and monitoring HER2 expression state of breast cancer in the future.
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Authors | Dong-Li Li, Jian-Er Tan, Ying Tian, Shun Huang, Peng-Hui Sun, Meng Wang, Yan-Jiang Han, Hong-Sheng Li, Hu-Bing Wu, Xing-Mei Zhang, Yi-Kai Xu, Quan-Shi Wang |
Journal | Biomaterials
(Biomaterials)
Vol. 147
Pg. 86-98
(Dec 2017)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 28938164
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved. |
Chemical References |
- Ferric Compounds
- Magnetite Nanoparticles
- Molecular Probes
- Recombinant Proteins
- Receptor, ErbB-2
- Trastuzumab
- Fluorescein
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Topics |
- Animals
- Ankyrin Repeat
- Breast Neoplasms
(diagnostic imaging, metabolism)
- Cell Line, Tumor
- Cell Survival
- Female
- Ferric Compounds
(chemistry)
- Fluorescein
(chemistry)
- Heterografts
- Humans
- Magnetite Nanoparticles
(chemistry)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Molecular Probes
(chemistry)
- Neoplasm Recurrence, Local
(diagnostic imaging)
- Neoplasm Transplantation
- Particle Size
- Receptor, ErbB-2
(metabolism)
- Recombinant Proteins
(chemistry)
- Surface Properties
- Trastuzumab
(pharmacology)
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