کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6450539 | 1416120 | 2017 | 13 صفحه PDF | دانلود رایگان |
- Multifunctional nanoparticles (SPIO-G3-5MF) are successfully synthesized.
- SPIO-G3-5MF selectively and efficiently binds to HER2 in vitro and in vivo.
- SPIO-G3-5MF is capable of binding to HER2 even in the presence of Trastuzumab.
- SPIO-G3-5MF yields remarkable T2 signal reduction in HER2-posivetive tumor in vivo.
- Long and effective tumor retention from 6 to 24Â h post-injection was verified.
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.
Journal: Biomaterials - Volume 147, December 2017, Pages 86-98