Magnetic nanoparticles (MNPs) have been used in various areas, such as in the manufacture of bearings, seals, lubricants, heat carriers, and in printing, recording, and polishing media.[1] One of the rapidly developing research subjects involving MNPs is their application in biological systems, including their application in magnetic resonance imaging (MRI), targeted drug delivery, rapid biological separation, biosensors, and magnetic hyperthermia therapy.[2] The exploration of the interaction between nanostructured materials and living systems is of fundamental and practical interest, and it opens new doors to novel interdisciplinary research field,“nanobioscience”. MNPs exhibited great potential for in vitro and in vivo biomedical application,[3] and the biodistribution of MNPs is strongly influenced by their size, charge, and surface chemistry.[4] Recently published reports indicate that magnetic nanoparticles (or microparticles), Fe3O4, conjugated with various targeting molecules or antibodies, can be used to target specific cells in vitro.[5] However, the noncovalent surface modification of nanoparticles has a serious limitation for biological applications, because the exposed metal ion on the surface of nanoparticles can cause metal elemental toxicities in cells (in vivo model).[6] To address this issue, our research has been focused on the development of suitable biocompatible materials for surface coating of nanoparticles. Silica (SiO2) was selected for surface modification of MNPs because it is a good biocompatible material and resistant to decomposition invivo.[7] Hence, silica-coated core–shell nanoparticles have been extensively studied over the past decade,[8] and these were recently synthesized with a functionalized surface for bioconjugation through various simple methods for application [9] in biological systems. To improve the versatility of silicacoated core–shell nanomaterials, an organic fluorescent dye was incorporated into the silica shell. Thus, the magnetic and fluorescence properties enables dual detection of the silica-coated core–shell magnetic nanoparticles (MNP@ SiO2).[10] The additional advantage provided by the incorporation of a fluorescent dye into the silica shell is the significant increase in photochemical stability, resulting in minimal photobleaching even after multiple exposures, which is currently a topic of great importance among researchers using confocal laser scanning microscopy (CLSM). It was also reported that the organic dye encapsulated in the silica-coated core–shell architecture results in increased fluorescence intensity due to “caging effects”.[11] Therefore, fluorescence hybrid core–shell MNPs are attractive candidates for various biomedical applications. We recently reported the synthesis of organic dye-incorporated silicacoated core–shell MNPs {MNP@ SiO2 (OD) s, OD: organic dye} that had controllable shell thickness and could be taken up by various cells. These MNP@ SiO2 (OD) s nonspecifically taken up by cells could be moved in the direction of an externally applied magnetic field, referred to as the “magnetic motor effect”.[10b, 12] In this study, the silica shell of the MNP@ SiO2 incorporated with commonly used organic dyes (rhodamine B isothiocyanate, RITC, orange color, maximum emission wavelength (lmax (em.))= 555nm, or fluorescein isothiocyanate, FITC, green color, lmax (em.)= 518nm) were modified with various functional organosilicon compounds (Si compounds), such as (MeO) 3Si-PEG(2-[methoxy (polyethyleneoxy) propyl] trimethoxysilane: CH3O (CH2CH2O) 6–9-CH2CH2CH2Si (OCH3) 3) and APS(3-aminopropyltriethoxysilane:(EtO) 3SiÀ (CH2) 3NH2). The surface of the dual …