Silica Nanoparticles Promote the Megakaryocyte Maturation and Differentiation: Potential Implications for Hematological Homeostasis

Silica nanoparticles (SiO₂ NPs) have been widely applied in diverse areas, thus causing the extensive release through multiple routes. Their toxicological effects, especially for the disturbance in hematological homeostasis, have raised public concern. Considering the detrimental role of excessive platelets in many cardiovascular diseases, the regulation of platelet formation offers a unique aspect for studying the blood compatibility of nanomaterials. In this study, the effects of SiO₂ NPs with four sizes (80, 120, 200, and 400 nm) were investigated on the maturation and differentiation of the megakaryocytes into platelets. The results showed that SiO₂ NPs promoted megakaryocyte development as manifested by the occurrence of irregular cell morphology, enlargement of cell size, increases in DNA content and DNA ploidy, and formation of spore-like protrusions. The expression of megakaryocyte-specific antigen (CD41a) was up-regulated, due to SiO₂ NP treatments. The correlation analysis of SiO₂ NP size with the above test bioindicators showed that the smaller the SiO₂ NPs were, the stronger effects they induced. Moreover, exposure to SiO₂ NPs induced the up-regulation of both GATA-1 and FLI-1, while the transcriptional expressions of aNF-E2 and fNF-E2 remained unchanged. The significant positive correlation of GATA-1 and FLI-1 with megakaryocytic maturation and differentiation suggested their crucial roles in the SiO₂ NP-promoted effect. The finding herein provided new insight into the potential health risk of SiO₂ NPs by perturbing the platelet-involved hematological homeostasis.