Multifunctional superparamagnetic nanoparticles conjugated with fluorescein-labeled designed ankyrin repeat protein as an efficient HER2-targeted probe in breast cancer.

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.

• 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)
• 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

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)