Development and evaluation of a Cu(II) complex as nanosuspension for enhanced antitumor efficacy against glioblastoma cancer

The clinical application of the metal complexes with promising anticancer activity is limited due to their extremely poor water solubility. To circumvent this, approaches based on drug delivery systems are routinely examined. Herein, an aqueous nanosuspension of a Cu(II) complex, [Cu(^2MeObpy)₂](PF₆)₂ where ^2MeObpy is 4,4'-dimethoxy-2,2'-bipyridine, was prepared and stabilized with the non-ionic polysorbate 60 (Tween 60) (TW60) by using an antisolvent precipitation method. The optimized formulation (CuTW60-NS) was characterized by FT-IR, UV-Vis, dynamic light scattering (DLS), X-ray diffraction (XRD) analysis, thermal analyses, and field emission scanning electron microscopy (FE-SEM) in comparison with its Cu-S counterpart (water suspension). Anticancer activity of CuTW60-NS was compared with the Cu(II) complex dissolved in DMSO (Cu-DMSO) and Cisplatin towards the human glioblastoma cancer cells (U-87) via a series of cellular and molecular techniques. CuTW60-NS showed a reduced particle size in the range of 400-700 nm along with high solubility and long-term stability. CuTW60-NS exhibited more efficient cytotoxicity against U-87 after 48 h than Cu-DMSO with IC₅₀ of 7.8 ± 0.7 µg/ml, a 2-fold reduction. High antimetastatic activity of CuTW60-NS against U-87 cells was observed through inhibition of cell migration and colony formation. CuTW60-NS promoted apoptotic cell death (70-80%), further confirmed through molecular studies by regulation of apoptotic-relevant BAX and BCL2 genes. This work presents the CuTW60-NS formulation as a promising anticancer agent, in view of the excellent improvement in its physicochemical and biological properties. In the end, this study opens a window to the development of the novel nanosuspension-based delivery systems for insoluble metal complexes in cancer therapy.