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Silica-encapsulated nanospheres of water-soluble ferrocene complexes WFCs@SiO2 and WFCs@SiO2@glutaraldehyde (GA) were first synthesized by a facile inverse-microemulsion method. The surface functional groups, particle size, and morphologies of nanospheres were characterized by IR spectra, UV–vis absorption spectra, dynamic light scattering (DLS) and SEM images. Single-crystal X-ray diffraction was used to confirm the molecular structure of free ferrocenyl-pyrazol ligand (L) and three WFCs, namely, [Ni(C22H14F6FeN4O4)(H2O)4] (5a), [Mg(C22H14F6FeN4O4)(H2O)4]·3H2O (5b), and [Ba(C22H14F6FeN4O4)(H2O)3] (5c). The electrochemical properties of 5a–5c were explored by cyclic voltammetry. The WFCs-loading capacities of 5a–5c in WFCs@SiO2 were found to be 38.4, 38.2, and 38.1 μg/mg, respectively. Cell studies under two drug delivery modes (free diffusion and endocytosis) were carried out by MTT cell-survival assays and morphological observation of HepG2 cells. It's interesting that the cytotoxicity of WFCs against HepG2 was increased by applying silica nanocarriers. Compared to WFCs@SiO2, the modification of GA on the spherical surface provided not only the better water-dispersity but also additional functional groups for further modification of other pharmacophores. The novel nanocarrier system for WFC delivery present a novel concept-of-proof method to protect varieties of affordable metal-based anticancer agents in physiological conditions and provided experimental basis for future studies focusing on drug delivery of other WFCs.
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•Three water-soluble ferrocene complexes (5a–5c) were designed and synthesized.•An alternative approach to protect ferrocene complexes from adverse environments is proposed.•Other metal-based anticancer agents can also be encapsulated in silica nanospheres with the use of this approach.