Fixed Bed Reactor for Solid-Phase Surface Derivatization of Superparamagnetic Nanoparticles
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文摘
The functionalization of nanoparticles is conditio sine qua non in studies of specific interaction with a biologicaltarget. Often, their biological functionality is achieved by covalent binding of bioactive molecules on a preexistingsingle surface coating. The yield and quality of the resulting coated and functionalized superparamagnetic ironoxide nanoparticles (SPIONs) can be significantly improved and reaction times reduced by using solid-phasesynthesis strategies. In this study, a fixed bed reactor with a quadrupole repulsive arrangement of permanentmagnets was assayed for SPION surface derivatization. The magnet array around the fixed bed reactor createsvery high magnetic field gradients that enables the immobilization of SPIONs with a diameter as low as 9 nm.The functionalization on the surface of immobilized 25 nm 3-(aminopropyl)trimethoxysilane-coated SPIONs (APS-SPIONs) was performed using fluorescein-isothiocyanate directly, and by the SV40 large T-antigen nuclearlocalization signal peptide (PKKKRKVGC) conjugated to acryloylpoly(ethylene glycol)-N-hydroxysuccinimide,where the PEG reagent is conjugated first to create a functionalized nanoparticle and the peptide is added to theacryloyl group. We show that the yield of reactant grafted on the surface of the APS-coated SPIONs was higherin solid-phase within the fixed bed reactor compared to conventional liquid-phase chemistry. In summary, thefunctionalization of SPIONs using a magnetically fixed bed reactor was superior to the liquid-phase reaction interms of the yield, reaction times required for derivatization, size distribution, and scalability.

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