Facile Functionalization and Phase Reduction Route of Magnetic Iron Oxide Nanoparticles for Conjugation of Matrix Metalloproteinase

A protocol for the simultaneous functionalization and phase reduction route of iron oxide magnetic nanoparticles (MNPs) and its further bioconjugation is presented. It was found that surface functionalization of maghemite (γ‐Fe2O3) nanoparticles with mercaptopropyltrimethoxysilane (MPTMS) under anoxic environment at above 80 °C promotes in situ conversion to magnetite (Fe3O4). Full conversion to Fe3O4, as probed by Mössbauer spectroscopy, with accompanied increase in the composite saturation magnetization, was achieved at 120 °C. By controlling the MPTMS concentration, the resultant silane‐MNPs morphology can be tuned from having homogeneous thin layer (<1 nm) to thick continuous silane with embedded MNP multicores. Likewise the amount of surface distal thiol moieties was dependent on the silanization conditions. The density of distal thiols (i.e., amount of thiol per surface area) and resultant aggregate size have direct impact on the attachment, as well as the activity and reusability of the conjugated matrix metalloproteinase (MMP‐2, using sulfo‐SMCC as crosslinker). The work has important implication to the field of magneto‐chemotherapeutics, where spatial control of conjugated active biomolecules under magnetic field and T2‐weighted MRI contrast can be achieved simultaneously.