Integrative proteomics and metabolomics analysis reveals the toxicity of cationic liposomes to human normal hepatocyte cell line L02

Cationic liposomes (CLs) are vital nonviral vectors with a wide range of applications. Although the toxicity of CLs is far lower than that of viral vectors, increasing evidence suggests that there are limited clinical applications of CLs because of their potential toxicity. In the present study, the toxicity of CLs toward L02 cells was investigated and comprehensively analyzed based on proteomics and metabolomics data. Using quantitative iTRAQ-LC-MS/MS proteomics coupled with UHPLC-Q-TOF-MS based metabolomics, we determined that exposure to CLs generated 90 significantly altered proteins and 65 altered metabolites in cells. Metabolomic analysis also showed significant alterations in metabolic pathways, including small molecules involved in energy and lipid metabolism. Proteomics revealed that exposure to CLs significantly influenced multiple proteins, including those involved in the folding of proteins and metabolism. Furthermore, the proteins participated in oxidative stress, which also influenced lipid metabolism. Overall, our findings indicate that high-throughput metabolomics and proteomics can provide insight into the toxicological mechanisms of CLs using high-resolution mass spectrometry. To our knowledge, this is the first study combining proteomics and metabolomics to investigate the potential effects of CLs on any cells. Specifically, we integrated quantitative iTRAQ-based proteomics with UHPLC-Q-TOF-MS-based metabolomics datasets to comprehensively assess the potential mechanisms of CL toxicity towards L02 cells.