Surface Modification of Magnetic Nanoparticles for Bio-application

MasterMagnetic nanoparticles (MNPs) have been intensively investigated for in vitro and in vivo applications such as a contrast agent for magnetic resonance imaging and magnetically guided drug delivery vehicles due to their unique magnetic properties, biocompatibility and lack of toxicity. Also, they can be served as magnetic separation platform for specific biomolecules. The magnetic separation of specific compound is more efficient and convenient than other separation method. To achieve efficient and practical MNP-based bioseparation, MNPs should have high colloidal stability in physiological condition and minimal non-specific adsorption with biomolecules except target molecules. In this work, synthesis and surface modification of MNPs were described. At first, the fabrication of silica-shell-coated magnetic nanoparticle cluster (SMNC) and successive surface engineering onto SMNC to produce surface-modified SMNC with zwitterionic and primary amine ligands (SMNC-ZW/Am) were showcased. SMNC-ZW/Am is passivated by zwitterionic ligands for improved colloidal stability and reduced non-specific adsorption, and primary amine ligands for simple conjugation with biomolecules. The colloidal characteristics, based on the hydrodynamic size and zeta potential, of SMNC-ZW/Am could be flexibly tuned by controlling the relative amount of zwitterionic and primary amine ligands. SMNC-ZW/Am showed enhanced colloidal stability in high salt concentration and broad pH range rather than did bare SMNC. In addition, non-specific adsorption with biomolecules onto SMNC-ZW/Am surface was significantly suppressed owing the zwitterionic ligands. Reduced non-specific adsorption was confirmed using photoluminescence based protein adsorption assay. Bioconjugation capability of SMNC-ZW/Am could be achieved by using primary amine groups on SMNC-ZW/Am surface, which allowed facile bioconjugation with biotin. Using streptavidin bead and streptavidin-conjugated quantum dot assay, we confirmed that biotins could be successfully conjugated onto surface of SMNC-ZW/Am, and this bioconjugation capability onto colloidal SMNCs with reduced non-specific adsorption should be useful as magnetically-controllable nanosubstrate. Using these surface-modification strategies with zwitterionic moieties, MNPs could be empowered to have higher colloidal stability and more readily conjugated with biomolecules as highly reproducible and useful nanoplatform in various other types of bioseparation and bioanalytical applications. Also, MNPs can be also embedded in various platforms including polymer matrix and mesoporous silica, which provides the advantages of post-functionalizations. The introduction of MNPs to various platforms requires the surface modification to the appropriate type of the ligands. Through the ligand exchange, the MNPs that can be dispersed in aqueous phase and interact with cucurbit[6]uril polymer nanocapsule (CB-PN) platform were developed. CB-PN shows hollow and spherical structure that consists of the disk-shaped molecules with a cavity. The CB-PN can be served as a platform where various nanoparticles are introduced on the surface for many applications. MNPs were initially synthesized in organic solvent using thermal decomposition method for their monodispersity and for the desired size (for high MRI contrast). One phase ligand exchange was conducted with the synthesized MNPs using two hydrophilic ligands; 3,4-dihydroxyhydrocinnamic acid (DHCA) and DHCA-derivative (spermidine) molecule. The amine group of spermidine could interact with the cucurbit[6]uril. The DHCA-spermidine molecules on the surface of MNPs were used as an anchor to connect CB-PN. The ligand-exchanged MNPs have the dispersion stability in aqueous phase and sufficient interaction to link the CB-PN through the method of simple mixing between CB-PN and MNPs, which was confirmed by the measurement of dynamic light scattering and transmission electron microscopy. On the magnetic properties of MNPs, the SMNC-ZW/Am and MNPs@CB-PN could be potential candidates for biological applications such as bioseparation platform and magnetic resonance imaging