Synthesis, cytotoxicity and antitumour mechanism investigations of polyoxometalate doped silica nanospheres on breast cancer MCF-7 cells

摘要

Polyoxometalates (POMs) have shown the potential anti-bacterial, anti-viral and anti-tumor activities. In order to improve their physiological stability and antitumour activity for medical application, K2Na[As^IIIMo6O21(O2CCH2NH3)3]·6H2O doped silica nanospheres (POM@SiO2) with diameters of ~40 nm have been synthesized by the water-in-oil microemulsion method in this study. The obtained spheres were morphologically uniform nanosized and nearly monodispersed in solution. The nanoparticles had high entrapment efficiency, which was upto 46.2% by the inductively coupled plasma mass spectrometry (ICP-MS) analysis and POMs slowly released from the nanospheres both in the PH 7.4 and 5.5 phosphate buffer saline (PBS) solutions in 60 h. The in vitro MTT assays of particles on MCF-7 cell line (a human breast adenocarcinoma cell line) exhibited enhanced antitumor activity compared to that of plain polyoxometalate. The IC50 value of the POM@SiO2 nanoparticles was 40.0 μg/mL at 24 h calculated by the encapsulated POM concentration, which was much lower comparing to that of 2.0 × 10⁴ μg/mL according to the pure POM. And the SiO2 shells showed low inhibitory effect at the corresponding concentration. Confocal images further indicated the cell morphology changes and necrosis. Flow cytometric analysis showed nanoparticles induced the apoptosis by arresting the cells in S phase and western blot analysis indicated they promoted apoptosis by inhibiting the Bcl-2 protein. Moreover, the study of interactions between human serum albumin (HSA) and the nanoparticles indicated the fluorescence quenching was static, and the nanoparticles were likely to bind to HSA and changed its conformation.