Gadolinium-containing bioparticles as an active entity to promote cell cycle progression in mouse embryo fibroblast NIH3T3 cells

In the present study, we demonstrated that gadolinium-containing particles formed in cell culture medium acted as a biologically active entity to mediate cell cycle progression in NIH3T3 cells. The particles were observed to accumulate at the cell surface by scanning electron microscopy. Energy-dispersive X-ray analysis was undertaken and confirmed that gadolinium was incorporated in the agglomerated particles. Moreover, the smaller gadolinium particles exhibited a stronger cell-cycle-promoting effect than the larger ones, but they shared the common signaling pathways. Both extracellular signal regulated kinase and phosphatidylinositol 3-kinase signaling pathways were activated by gadolinium-containing particles and may account for their proliferation-promoting effect on NIH3T3 cells. Furthermore, the study showed that the free gadolinium ion released from gadolinium-containing particles may be responsible for the proliferation effect. This study will be helpful to clarify the biological effect of the insoluble species formed from Gd3+ as well as other multivalent metal ions under physiological conditions and will help to improve their medical applications.