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.

中文翻译：

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多功能超顺磁性纳米粒子与荧光素标记的设计锚蛋白重复蛋白偶联，可作为乳腺癌有效的HER2靶向探针

基于原发性和转移性/复发性乳腺癌之间人类表皮生长因子受体2（HER2）表达的差异，具有系统评估和动态监测HER2表达潜能的HER2分子成像可能会改善患者抗- HER2治疗。在这项研究中，使用设计的锚蛋白重复蛋白（DARPin）G3，一种对HER2具有皮摩尔亲和力的新型结合蛋白，并开发了用荧光素5-马来酰亚胺标记的DARPin G3（SPIO-G3-5MF）修饰的多功能超顺磁性纳米颗粒，用于HER2成像。我们的结果表明，即使在存在曲妥珠单抗的情况下，SPIO-G3-5MF纳米粒子也具有约100 nm的均匀大小，良好的分散性和低细胞毒性，可以选择性地与HER2阳性乳腺癌细胞结合。生物分布测定表明，尽管一部分SPIO-G3-5MF纳米颗粒不可避免地被肝脏和脾脏捕获，但在HER2阳性移植乳腺肿瘤中仍观察到SPIO-G3-5MF的大量积累和长期保留。进一步的MR成像显示SPIO-G3-5MF可以选择性地对HER2阳性移植乳腺肿瘤进行成像，从而产生显着效果T ₂信号降低（6 h时为50.33±2.90％，24 h时为47.29±9.36％）。我们的研究表明，SPIO-G3-5MF可能是未来诊断和监测乳腺癌HER2表达状态的有前途的MR分子探针。