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

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 Trichophyton rubrum, 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.