LAUSR

Abstract The prevalence of functionalized nanoparticles in biological and clinical fields attracts intensive toxicology investigations. Minimizing the nanoparticles’ biohazard remains a challenge due to the insufficient understanding on the nanoparticle-induced cell death mechanism. In the presented study, we observed the lysosome and genome injuries and so caused cell cycle changes and regulations of retinal ganglion neuron cell 5 (RGC-5) induced by aminated and alkylated nanoparticles. Alkylated nanoparticles induced malignant lysosome and genome damages followed by severe post-self-repair responses. RGC-5 treated with alkylated nanoparticles presented dramatic S phase prolongation resulted from cyclin E accumulation mediated by Fbw7 downregulation, which assisted DNA replication after failed self-repair of the malignantly damaged DNA caused by alkylated nanoparticles. Differently, aminated nanoparticles in RGC-5 induced moderate lysosome and genome injuries and these damages could be repaired in the p21-involved pathway, so that cells did not induce apparent cyclin E accumulation nor Fbw7 downregulation as post-self-repair response. These results helped us to understand the toxicity of analogous nanoparticles on retinal ganglions such as glaucoma treatment. This work provides new insights into nanoparticle functionalization and toxicity in relation to the research on the toxicology and pathology of nerve cells.