Aimed at utilizing high-magnetization nanospheres for magnetic field-enhanced cellular labeling, core-shell structured sandwich-like magnetic mesoporous silica nanospheres were developed. While the magnetite cluster core can provide a high magnetic response for overcoming Brownian motion in cell culture media, the layered silica shell facilitates an efficient fluorescent dye labeling. However, the problem of particle aggregation in cell media, which is strongly enhanced under a magnetic field, significantly impeded the uptake by cells, resulting in difficulties in the precise analysis of the degree of particle internalization by fluorescence-based techniques (flow cytometry and confocal microscopy). To overcome this, reflection-based assessment was employed. Further, emphasis was put on utilizing the unique role of surface-hyperbranched polyethylenimine (PEI) in efficient prevention of particle aggregation prior to cell internalization in the presence of an external magnetic field. The interparticle attraction forces originating from magnetic dipole-dipole interactions are hereby balanced by the steric and electrostatic repulsion forces provided by the PEI functionalization, which leads to dispersed nanospheres in cell culture media during the magnetic-field induced cell labeling. As a consequence, PEI functionalization and the presence of the magnetic field synergistically enhanced the efficiency of MRI-fluorescence dual-mode labeling for cellular tracking.
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