Positively Charged Nanoplastics Destruct the Structure of the PCK1 Enzyme, Promote the Aerobic Gycolysis Pathway, and Induce Hepatic Tumor Risks

The production and weathering processes of nanoparticles (NPs) introduce charged functional groups on their surface. Previous studies have found that the surface charge properties of NPs play a critical role in their toxic effects and the mechanisms are generally attributed to their different accumulations and transmembrane potentials. Currently, we still lack sufficient knowledge about effects, owing to the unique structures of these polymers. In this study, positively charged NPs (PS-NH₂, 50 nm) at 0.05-0.5 μg mL^-1 promoted the proliferation of hepatic tumors in oncogenic <i>Kras</i>^<i>G12V</i> zebrafish larvae and they also increased the viability of human hepatocellular carcinoma cells, whereas negatively charged NPs (PS-COOH, 50 nm) did not. We present evidence indicating that the potential carcinogenicity of PS-NH₂ is related to the special polymer-molecular interactions caused by its positive surface charge. The affinity of PS-COOH chains for peptides typically enhances enzyme stability and upregulates its expression. However, PS-NH₂ strongly competes with hydrogen bonds of the first rate-limiting enzyme PCK1 in gluconeogenesis, thus downregulating the expression of PCK1 and promoting the aerobic glycolysis pathway, which most tumor cells prefer. This study indicates that positive-charge modified NPs in the environment may bring additional carcinogenic risks.