Green, scalable, low cost and reproducible flow synthesis of biocompatible PEG-functionalized iron oxide nanoparticles
Green, scalable, low cost and reproducible flow synthesis of biocompatible PEG-functionalized iron oxide nanoparticles
复制标题
绿色、可扩展、低成本和可重复的生物相容性聚乙二醇功能化氧化铁纳米颗粒的流动合成
DOI：
10.1039/d1re00239b
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发表时间：
2021-07-29
影响因子：
3.9
通讯作者：
Torrente-Murciano, Laura
中科院分区：
文献类型：
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作者：
Mahin, Julien;Franck, Christoph O.;Torrente-Murciano, Laura
功能化氧化铁纳米颗粒具有广泛的生物医学应用前景。然而，在适当的表面涂层上大规模地制造这些纳米颗粒以使其完全稳定和生物相容性仍然是一个相当大的挑战。为了克服这一问题，本文提出了一种使用模块化微反应器系统的合成和功能化的新组合，避免了中间配体交换步骤的需要。连续流动技术可以在温和的条件下在水中重现合成裸氧化铁纳米颗粒（7 +/- 2 nm），同时使用定制的异双功能PEG稳定剂进行快速高效的功能化。通过简单的酰胺偶联，纳米颗粒可以很容易地与任何感兴趣的分子衍生，证明了它们作为生物医学应用的多功能平台的能力。根据LDH细胞毒性试验，制备的氧化铁纳米颗粒具有完全的生物相容性，在各种生物相关介质中高度稳定，适用于T-2 MRI对比应用(r(1) = 1.44 mM(-1) s(-1), r(2) = 272 mM（-1) s(-1)）。完整的成本分析揭示了该工艺的商业可行性，总成本低至506克（-1）英镑，证明了这种模块化方法在实际应用中大规模部署功能化纳米材料的潜力。
Functionalized iron oxide nanoparticles are of great interest for multiple biomedical applications. However, it remains a considerable challenge to manufacture these nanoparticles reproducibly on a large scale with the appropriate surface coating to render them completely stable and biocompatible. To overcome this problem, a novel combination of synthesis and functionalization using modular microreactor systems is presented here, avoiding the need of intermediate ligand exchange steps. Continuous flow technology enables reproducible synthesis of bare iron oxide nanoparticles (7 +/- 2 nm) in water under mild conditions, in tandem with extremely fast and efficient functionalization with a custom heterobifunctional PEG stabilizer. The nanoparticles can be easily derivatized with any molecule of interest through simple amide coupling, demonstrating their capacity to act as a versatile platform for biomedical applications. The produced iron oxide nanoparticles are fully biocompatible based on a LDH cytotoxicity assay, highly stable in various biologically relevant media and suitable for T-2 MRI contrast applications (r(1) = 1.44 mM(-1) s(-1), r(2) = 272 mM(-1) s(-1)). A full cost analysis reveals the commercial viability of the process, with a total cost as low as pound 506 g(-1), demonstrating the potential of this modular approach to enable the large-scale deployment of functionalized nanomaterials in real world applications.