Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence

Mesoporous silica nanoparticles (MSNs) are widely usedin the biomedicalfield because of their unique and excellent properties. However, thepotential toxicity of different shaped MSNs via injection has notbeen fully studied. This study aims to systematically explore theimpact of shape and shear stress on the toxicity of MSNs after injection.An in vitro blood flow model was developed to investigate the cytotoxicityand the underlying mechanisms of spherical MSNs (S-MSN) and rodlikeMSNs (R-MSN) in human umbilical vein endothelial cells (HUVECs). Theresults suggested that the interactions between MSNs and HUVECs underthe physiological flow conditions were significantly different fromthat under static conditions. Whether under static or flow conditions,R-MSN showed better cellular uptake and less oxidative damage thanS-MSN. The main mechanism of cytotoxicity induced by R-MSN was dueto shear stress-dependent mechanical damage of the cell membrane,while the toxicity of S-MSN was attributed to mechanical damage andoxidative damage. The addition of fetal bovine serum (FBS) alleviatedthe toxicity of S-MSN by reducing cellular uptake and oxidative stressunder static and flow conditions. Moreover, the in vivo results showedthat both S-MSN and R-MSN caused cardiovascular toxicity in zebrafishand mouse models due to the high shear stress, especially in the heart.S-MSN led to severe oxidative damage at the accumulation site, suchas liver, spleen, and lung in mice, while R-MSN did not cause significantoxidative stress. The results of in vitro blood flow and in vivo modelsindicated that particle shape and shear stress are crucial to thebiosafety of MSNs, providing new evidence for the toxicity mechanismsof the injected MSNs.