Polyoxometalates nanoparticles improve anti-tumor activity by maximal cellular uptake

Abstract

The development of polyoxometalates (POMs) nanoparticles (NPs) as a new generation anti-cancer drugs to realize enhanced diagnoses and treatment outcomes is highly desirable but remains a great challenge. In this work, four kinds of small sizes polyoxometalates nanoparticles (NH4)11.9[Nd4.7(MoO4)(H2O)23(Mo7O24)4]·19H2O, (POM1-NP) (NH4)28[Ce8(MoO4)2(H2O)31(Mo7O24)8]·74H2O, (POM2-NP) (NH4)11.9[Pr4.7(MoO4)(H2O)23(Mo7O24)4]·34H2O (POM3-NP) and (NH4)26[CoPr8(MoO4)2(H2O)31(Mo7O24)8]·54H2O (POM4-NP) with the average particle diameters of about 50 ± 5 nm synthesized by a simple and environmental friendly freeze-drying method can be easier taken up by cells and show higher cytotoxicity against six human cancer cell lines compared with (NH4)11.9[Nd4.7(MoO4)(H2O)23(Mo7O24)4]·19H2O (POM1), (NH4)28[Ce8(MoO4)2(H2O)31(Mo7O24)8]·74H2O (POM2), (NH4)11.9[Pr4.7(MoO4)(H2O)23(Mo7O24)4]·34H2O (POM3) and (NH4)26[CoPr8(MoO4)2(H2O)31(Mo7O24)8]·54H2O (POM4) prepared by hydrothermal method. Most obviously, the IC50 of POM4-NP on Hela cells is 0.042 μmol increased by 2.5-fold than POM4 with the IC50 value of 0.105 μmol and 38-fold than (NH4)6[Mo7O24] ([Mo7O24]6−) with the IC50 value of 1.618 μmol, the anti-tumor activity of which has been greatly improved. POMs 1-4 NPs revealed stronger penetration and lower side effects of dose-dependent by cellular uptake compared with POMs 1-4. It proves that the POMs 1-4 and POMs 1-4 NPs have good stability for 24 h by UV-vis and SEM. Further studies on its mechanism have shown that POMs can arrest cell cycle and induce apoptosis in MCF-7 cells. These studies will supply direction for developing NPs for intervention therapy against relevant cancers and also have implications in determining nanotoxicity.