Surface Modificated and Multifunctional Iron Oxide Nanostructures Construction for Bioapplications

Abstract

Magnetic iron oxide nanoparticles (Fe3O4 NPs, IONPs) represent a prominent class of multifunctional nanomaterials that have been increasingly explored for diverse biomedical applications, such as magnetic resonance imaging (MRI), biological catalysis (nanozyme), magnetic hyperthermia, magnetic targeting and separation, photothermal therapy, and drug transport. Owing to their large surface-to-volume ratio and high surface energy, IONPs have a natural tendency to aggregate in order to minimize the system’s surface energy. In addition, the uncoated particles are chemically reactive and readily oxidized in air. Therefore, surface modification of IONPs is essential—not only to enhance their stability by preventing aggregation and oxidation but also to create a versatile interface for further functionalization. This dissertation focuses on developing strategies for surface engineering and multifunctionalization of IONPs to enable biomolecular conjugation and broaden their biomedical applications. Chapter 2 presents the develop of a multidentate catechol-based copolymer for 7 nm-sized IONPs. Using an amine-assisted catechol nanocoating (ligand-exchange) approach, compact, monodisperse, and highly colloidally stable IONPs grafted with the designed multifunctional brush polymer were successfully obtained. Subsequently, the conjugation of DNA strands onto the IONP surface was demonstrated, achieving an average “valency” ranging from 1 to 26 per particle, which enabled precise control over their spatial assembly. Furthermore, a series of core-satellite nanostructures (AuNP-IONP assemblies) were constructed through DNA hybridization using single-DNA-valency IONPs as building blocks. Finally, the T2 relaxivity was modulated by the distinct assembly configurations, which was attributed to the spatial arrangement-dependent aggregation of IONPs, hybrid spin-coupling interactions and local magnetic field fluctuations arising from electron-transfer dynamics within the nanostructure. In Chapter 3, a petal-like catalytic colorimetric nanohybrid was fabricated by the in situ growth of sub-nanometer Ruthenium nanoparticles on poly(acrylic acid)-functionalized 45 nm-sized magnetic iron oxide nanoflower supports (referred to as Ru-IONFs) and subsequently applied to enhance the sensitivity of lateral flow immunoassays (LFIAs). The incorporation of RuNPs not only improved the brightness of the colorimetric signal but also lowered the activation energy barrier, leading to an increased maximum reaction rate and enhanced peroxidase-like catalytic activity. As a proof of concept, the as-prepared Ru-IONFs nanozyme was integrated into LFIAs (Ru-IONFs-LFIAs) for the detection of SARS-CoV-2 antigen. Compared with conventional gold nanoparticle (AuNP)-based LFIAs, the Ru- IONFs-LFIAs exhibited a 20.5-fold enhancement in sensitivity, enabling a visual detection limit as low as 78 ng/mL. Given the outstanding analytical performance, the Ru-IONFs-based LFIA presents a promising and reliable platform for the rapid and sensitive diagnosis of SARS-CoV-2. As discussed earlier, we have developed highly stable and multifunctional magnetic iron oxide nanostructures through surface modification, enabling efficient biomolecule conjugation (including DNA and antibodies) for subsequent self-assembly and immunoassay applications. We believe that our strategy can significantly promote the broader bioapplication of IONPs, owing to their versatile and tailorable surface properties.