2026 Volume 51 Issue 8 Pages 403-411
The objective of this study was to examine the mechanisms underlying endocytic uptake, cytotoxicity, oxidative stress, and lysosomal damage caused by silica micro/nanoparticles (SiPs) in murine RAW-Blue macrophages. In parallel studies, we also assessed the effects of NF-κB on lysosomal membrane permeabilization (LMP). Three types of SiPs, 3 μm-plain (3 μm diameter particles without surface modification), 50 nm-plain (50 nm diameter particles without surface modification), and 50 nm-NH2 (50 nm diameter particles with an amine functional group as surface modification) were tested. A significant decrease in cell proliferation and a significant increase in cell death were evident, when cells were treated with 50 nm-plain. All types of SiPs plus a lysosomal inhibitor caused a significant increase and a significant decrease in cell proliferation and cell death, respectively. When cells were treated with 50 nm-plain, puncta formation was seen. Treatment with 50 nm-plain significantly increased the expression level of inflammatory cytokine/chemokine genes, whereas inhibitors of clathrin-mediated endocytosis, lysosomal function, and cathepsin activity significantly attenuated these responses. Taken together, the present findings suggest that lysosomal dysfunction is closely associated with 50 nm-plain-induced cytotoxic and inflammatory responses. Our findings also provide relevant findings for safe and effective design of SiPs and a framework to maximize their biomedical potential while mitigating lysosomal damage.
