Synthesis of 2-deoxy-d-glucose coated Fe3O4 nanoparticles for application in targeted delivery of the Pt(iv) prodrug of cisplatin – a novel approach in chemotherapy†
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Abstract
A water soluble Pt(IV) prodrug of cisplatin was synthesized by oxidation of cisplatin followed by treatment with succinic anhydride to achieve easily reducible ester linkage at axial positions which was evidenced from cyclic voltammetric analyses. Because of this modification the Pt(IV) prodrug achieved better physicochemical and pharmacological properties like water solubility and reduced toxicity for normal (non-cancerous) CHO cells respectively, as compared to cisplatin. Later, this Pt(IV) prodrug was loaded on 2-deoxy-D-glucose (2DG) functionalized over silica coated Fe3O4 magnetic nanoparticles (MNPs) to achieve the desired formulation. It exhibited potency as evidenced from the cytotoxicity evaluation against MCF-7 human breast cancer cell lines (IC50 ∼ 14 μM). This encouraged us to further study the percentage viability, apoptosis and cell death evaluations on MCF-7, Colo-205 and CHO cells by flow cytometry. The cytotoxic potency of the formulation towards cancer cells, Colo-205 and MCF-7 (22–30% apoptosis), was revealed while the parent formulation was non-toxic to non-cancerous, CHO cell lines (3% apoptosis) as compared to cisplatin. It revealed that the formulation is comparable to cisplatin in its cell killing efficiency. Additionally the FITC labeled MNPs coated with 2DG exhibited efficient cell uptake and fast internalization (within 3 h) accumulating mainly in the cytoplasm and at the cell surface. Besides this, the formulation exhibited heating efficacy suggesting its possible application for hyperthermia treatment also. These results indicate the possible utility of the formulation for site specific delivery of the Pt(IV) prodrug of cisplatin.
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