Wei Zhenzhen, Wu Yafeng, Zhao Yuewu, Mi Li, Wang Jintao, Wang Jimin, Zhao Jinjin, Wang Lixin, Liu Anran, Li Ying, Wei Wei, Zhang Yuanjian, Liu Songqin
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, People's Republic of China.
Laboratory of Bio-inspired Smart Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Anal Chim Acta. 2016 Sep 28;938:156-64. doi: 10.1016/j.aca.2016.07.037. Epub 2016 Jul 28.
Multifunctional nanoprobes with distinctive magnetic and fluorescent properties are highly useful in accurate and early cancer diagnosis. In this study, nanoparticles of Fe3O4 core with fluorescent SiO2 shell (MFS) are synthesized by a facile improved Stöber method. These nanoparticles owning a significant core-shell structure exhibit good dispersion, stable fluorescence, low cytotoxicity and excellent biocompatibility. TLS11a aptamer (Apt1), a specific membrane protein for human liver cancer cells which could be internalized into cells, is conjugated to the MFS nanoparticles through the formation of amide bond working as a target-specific moiety. The attached TLS11a aptamers on nanoparticles are very stable and can't be hydrolyzed by DNA hydrolytic enzyme in vivo. Both fluorescence and magnetic resonance imaging show significant uptake of aptamer conjugated nanoprobe by HepG2 cells compared to 4T1, SGC-7901 and MCF-7 cells. In addition, with the increasing concentration of the nanoprobe, T2-weighted MRI images of the as-treated HepG2 cells are significantly negatively enhanced, indicating that a high magnetic field gradient is generated by MFS-Apt1 which has been specifically captured by HepG2 cells. The relaxivity of nanoprobe is calculated to be 11.5 mg(-1)s(-1). The MR imaging of tumor-bearing nude mouse is also confirmed. The proposed multifunctional nanoprobe with the size of sub-100 nm has the potential to provide real-time imaging in early liver cancer cell diagnosis.
具有独特磁性和荧光特性的多功能纳米探针在癌症的准确早期诊断中非常有用。在本研究中，通过简便的改进Stöber方法合成了具有荧光SiO2壳层的Fe3O4核纳米颗粒（MFS）。这些具有明显核壳结构的纳米颗粒表现出良好的分散性、稳定的荧光、低细胞毒性和优异的生物相容性。TLS11a适配体（Apt1）是一种针对人肝癌细胞的特异性膜蛋白，可内化进入细胞，通过形成酰胺键作为靶标特异性部分与MFS纳米颗粒偶联。纳米颗粒上附着的TLS11a适配体非常稳定，在体内不会被DNA水解酶水解。荧光成像和磁共振成像均显示，与4T1、SGC - 7901和MCF - 7细胞相比，HepG2细胞对适配体偶联纳米探针的摄取显著。此外，随着纳米探针浓度的增加，处理后的HepG2细胞的T2加权MRI图像显著负增强，表明被HepG2细胞特异性捕获的MFS - Apt1产生了高磁场梯度。计算得出纳米探针的弛豫率为11.5 mg(-1)s(-1)。荷瘤裸鼠的MR成像也得到了证实。所提出的尺寸小于100 nm的多功能纳米探针有潜力在早期肝癌细胞诊断中提供实时成像。
