文献：Targeted Fe-doped silica nanoparticles as a novel ultrasound–magnetic resonance dual-mode imaging contrast agent for her2-positive breast cancer

文献链接：https://www.dovepress.com/targeted-fe-doped-silica-nanoparticles-as-a-novel-ultrasoundndashmagne-peer-reviewed-fulltext-article-IJN

作者：Xiaoyu li，shujun Xia，Wei Zhou，ri Ji，Weiwei Zhan

相关产品：Silane-PEG-COOH（硅烷-聚乙二醇-羧基）

原文摘要：

Background: Multimodal contrast agents with low toxicity and targeted modification have opened up new possibilities for specific imaging of breast cancer and shown broad application prospects in biomedicine and great potential for clinical transformation. In this work, a potential multifunctional imaging agent was developed by doping Fe into hollow silica nanoparticles (HS-Fe NPs), followed by modification with specific anti-HER2 antibodies, enabling the NPs to have dualmode ultrasound (US)–magnetic resonance (MR)-specific imaging capacity with low toxicity.

Methods: Anti-HER2 antibodies were conjugated to silane–polyethylene glycol (PEG)–COOHmodified HS-Fe (HS-Fe-PEG) NPs to produce HER2-targeted HS-Fe-PEG (HS-Fe-PEG-HER2) NPs. The toxicity of HS-Fe-PEG-HER2 NPs on targeted cells in vitro and blood and organ tissue of mice in vivo was investigated. Distribution in vivo was also studied. Confocal laser-scanning microscopy and flow cytometry were used to evaluate the targeting ability of HS-Fe-PEG-HER2 NPs in vitro. US and MR instruments were used for imaging both in vivo and in vitro.

Results: The obtained HS-Fe-PEG-HER2 NPs (average diameter 234.42±48.76 nm) exhibited good physical properties and biosafety. In solution, they showed obvious enhancement of the US signal and negative contrast in T2-weighted MR imaging. The binding rate of HS-Fe-PEGHER2 NPs to targeted cells (SKBR3) was 78.97%±4.41% in vitro. US and MR imaging in vivo confirmed that the HS-Fe-PEG-HER2 NPs were delivered passively into the tumor region of SKBR3 and bound specifically to tumor cells. Target enhancement was better than untargeted and targeted competition groups.

Conclusion: HS-Fe-PEG-HER2 NPs have potential as a low-cytotoxicity and dual-mode US–MR-specific imaging agent.   

Silane-PEG-COOH：Silane：硅烷是一类含有硅-氢键（Si - H）或硅-碳键（Si - C）等结构的化合物，在这个结构中主要起到表面修饰和连接的作用。硅烷具有能与无机材料表面（如玻璃、金属氧化物等）发生化学反应的特性，通过形成化学键（如硅氧键）牢固地附着在材料表面，从而为后续的修饰提供基础。PEG：聚乙二醇是具有良好水溶性、生物相容性和低poison性的聚合物。其分子链中的醚键（- O -）结构使得它具有柔顺性，并且能够在水中形成氢键，表现出良好的亲水性。PEG 部分在这里起到改善整个材料的亲水性、生物相容性以及增加分子链柔性的作用。COOH：羧基是一种具有化学活性的官能团，它可以参与多种化学反应，如酯化反应、酰胺化反应等。在 “Silane - PEG - COOH” 结构中，羧基主要用于和其他含有氨基（- NH2）或羟基（- OH）等官能团的分子进行反应，实现进一步的化学修饰或材料的功能拓展。基于Silane-PEG-COOH的性能，HS-Fe-PEG-HER2 NPs的合成如下：

图：合成及机制示意

HS-Fe-PEG-HER2 NPs的制备：

为激活HS-Fe-PEG NPs中的-COOH与抗her2抗体偶联，将 EDC和 NHS加入到 PBS中悬浮的EDC-PEG中。将混合物在一定温度下搅拌。为去除多余的EDC和NHS聚合物，用PBS离心。然后，将 HS-Fe-PEG和抗her2抗体悬浮于PBS中。振荡孵育后，用PBS离心，收集HS-Fe-PEG-HER2 NPs，洗涤，然后用PBS分散使用。

图：ζ电位

结论：

该文献成功制备出基于Silane-PEG-COOH合成的HS-Fe-PEG-HER2 NPs。所得的HS-Fe-PEG-HER2 NPs具有良好的物理性能和生物安全性。结果显示，HS-Fe-PEG-HER2 NPs具有作为低细胞poison性和双模式us-mr特异性显像剂的潜力。