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用于磁热疗、光热加热和抗真菌活性的生物相容性氧化铁纳米颗粒的多步无污连续流合成及聚乙二醇功能化

Multistep non-fouling continuous flow synthesis and PEG-functionalisation of biocompatible iron oxide nanoparticles for magnetic hyperthermia, photothermal heating and antifungal activity.

作者信息

Pal Sayan, Gkogkos Georgios, Piovesan Jacopo, Whiteley Zoe, Besenhard Maximilian O, Storozhuk Liudmyla, Lees Martin R, Thanh Nguyen Thi Kim, Craig Duncan Q M, MacRobert Alexander J, Murdan Sudaxshina, Gavriilidis Asterios

机构信息

Department of Chemical Engineering, University College London, Torrington Place, London, WC1E 7 JE UK.

Department of Biochemical Engineering, University College London, Bernard Katz Building, Gower St, London, WC1E 6BT UK.

出版信息

J Flow Chem. 2025;15(3):185-196. doi: 10.1007/s41981-025-00355-2. Epub 2025 Jun 2.

Abstract

An innovative method for synthesising and functionalising iron oxide nanoparticles (IONPs) with polyethylene glycol (PEG) using a continuous three-phase segmented flow reactor is presented. Integration of synthesis and functionalisation within a single reactor platform eliminates the need for laborious batch post-processing steps, such as washing, separation, and dialysis, significantly reducing processing time and enhancing efficiency. The incorporation of oleic acid during the PEG functionalisation step further improved colloidal stability, resulting in 15 nm nanoparticles that remained stable for months without precipitation. FTIR and TGA confirmed successful functionalisation, while XRD showed the absence of byproducts. The PEG-functionalised IONPs exhibited excellent biocompatibility, as confirmed by in vitro cytotoxicity assays, with cell viability exceeding 80% at biologically relevant concentrations. Importantly, the functionalisation process preserved the nanoparticles' key magnetic and thermal properties, such as saturation magnetisation, magnetic heating efficiency and photothermal response, which are essential for their application in therapeutic settings. Biomedical applications of these functionalised IONPs were explored across multiple domains. The nanoparticles showed efficient magnetic hyperthermia performance under an alternating magnetic field, making them suitable for cancer treatment via localised heating. Additionally, their photothermal properties were assessed under near-infrared (NIR) irradiation, demonstrating temperature rise proportional to concentration, and hence their potential for dual-mode therapeutic applications. Furthermore, antifungal activity assays revealed PEG-functionalised IONP's efficacy against , with complete fungal growth inhibition at specific concentrations, underscoring their potential in pharmaceutical antifungal formulations. The continuous flow process developed offers a robust platform for producing multifunctional nanoparticles tailored for biomedical applications, while ensuring compatibility with industrial-scale production demands.

摘要

介绍了一种使用连续三相分段流反应器用聚乙二醇(PEG)合成和功能化氧化铁纳米颗粒(IONPs)的创新方法。在单个反应器平台内集成合成和功能化消除了对诸如洗涤、分离和透析等费力的批量后处理步骤的需求,显著减少了处理时间并提高了效率。在PEG功能化步骤中加入油酸进一步提高了胶体稳定性,得到了15纳米的纳米颗粒,这些颗粒在数月内保持稳定而不沉淀。傅里叶变换红外光谱(FTIR)和热重分析(TGA)证实了功能化的成功,而X射线衍射(XRD)表明没有副产物。体外细胞毒性试验证实,PEG功能化的IONPs表现出优异的生物相容性,在生物学相关浓度下细胞活力超过80%。重要的是,功能化过程保留了纳米颗粒的关键磁性和热性能,如饱和磁化强度、磁热效率和光热响应,这些性能对于它们在治疗环境中的应用至关重要。探索了这些功能化IONPs在多个领域的生物医学应用。纳米颗粒在交变磁场下表现出高效的磁热性能,使其适用于通过局部加热进行癌症治疗。此外,在近红外(NIR)照射下评估了它们的光热性能,表明温度升高与浓度成正比,因此它们具有双模治疗应用的潜力。此外,抗真菌活性试验揭示了PEG功能化IONP对……的功效,在特定浓度下完全抑制真菌生长,突出了它们在药物抗真菌制剂中的潜力。所开发的连续流动过程提供了一个强大的平台,用于生产为生物医学应用量身定制的多功能纳米颗粒,同时确保与工业规模生产需求的兼容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15a7/12426144/237c6b37145b/41981_2025_355_Fig1_HTML.jpg

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