Insights of Platinum Drug Interaction with Spinel Magnetic Nanocomposites for Targeted Anti-Cancer Effect

SIMPLE SUMMARY: Magnetic ferrite nanocomposite has drawn huge interest in nanomedicine in areas related to thermotherapy, cell labeling-tracking and magnetic resonance imaging. Manganese ferrite spinel is an interesting magnetic nanocomposite due to its superparamagnetic nature, strong T2 MRI contrast, low synthesis cost, and eco-friendliness. The present study investigated the suitability of two different nanocarriers: one with a silica base (MnFe(2)O(4)/silica), and another with a carbon base (MnFe(2)O(4)/Graphene oxide) for targeted cancer therapy. The phase, textural and morphological variation of the two different nanoformulations was examined using various physico-chemical techniques. Pegylated and as-such nanoformulations were studied in drug delivery and in vitro using cancerous and non-cancerous cell lines. Density functional theory was used to calculate the binding energies between cisplatin on single-silica or multi-layered graphene oxide. Immunofluorescence images were captured using c-caspase 3/7 and TEM analysis. MnFe(2)O(4)/silica/cisplatin nanocomposites was found be a better chemotherapeutic drug delivery option than MnFe(2)O(4)/GO/cisplatin nanocomposites. ABSTRACT: In nanotherapeutics, gaining insight about the drug interaction with the pore architecture and surface functional groups of nanocarriers is crucial to aid in the development of targeted drug delivery. Manganese ferrite impregnated graphene oxide (MnFe(2)O(4)/GO) with a two-dimensional sheet and spherical silica with a three-dimensional interconnected porous structure (MnFe(2)O(4)/silica) were evaluated for cisplatin release and cytotoxic effects. Characterization studies revealed the presence of Mn(2+) species with a variable spinel cubic phase and superparamagnetic effect. We used first principles calculations to study the physisorption of cisplatin on monodispersed silica and on single- and multi-layered GO. The binding energy of cisplatin on silica and single-layer GO was ~1.5 eV, while it was about double that value for the multilayer GO structure. Moreover, we treated MCF-7 (breast cancer cells) and HFF-1 (human foreskin fibroblast) with our nanocomposites and used the cell viability assay MTT. Both nanocomposites significantly reduced the cell viability. Pt(4+) species of cisplatin on the spinel ferrite/silica nanocomposite had a better effect on the cytotoxic capability when compared to GO. The EC50 for MnFe(2)O(4)/silica/cisplatin and MnFe(2)O(4)/GO/cisplatin on MCF-7 was: 48.43 µg/mL and 85.36 µg/mL, respectively. The EC50 for the same conditions on HFF was: 102.92 µg/mL and 102.21 µg/mL, respectively. In addition, immunofluorescence images using c-caspase 3/7, and TEM analysis indicated that treating cells with these nanocomposites resulted in apoptosis as the major mechanism of cell death.