Fe₃O₄@OA@Poloxamer nanoparticles lower triglyceride in hepatocytes through liposuction effect and nano-enzyme effect

Lipid deposition induced various diseases including nonalcoholic fatty liver and hyperlipemia. The excessive accumulation of triglyceride (TG) and the deposition of fat were the two most critical causes. Here, we developed Fe₃O₄@OA@Poloxamer nanoparticles (NPs) with amphiphilic structures, which exhibited an excellent role in eliminating excess TG. Hydrophobic TG was adsorbed efficiently by Fe₃O₄@OA@Poloxamer NPs through the "liposuction effect" and the formation of NPs@TG complex was then conducted. The NPs@TG complex was further enclosed by the endosome based on the endocytosis and subsequently was taken into the lysosome, degrading with the help of lipases. Meanwhile, the "nano-enzyme effect" of Fe₃O₄ NPs recovered the lipid-regulated proteins including PPARα, further triggering biodegradation pathways of TG, although the lipid-regulated proteins were obviously inhibited in the high-fat hepatocytes models. These two mechanisms of Fe₃O₄@OA@Poloxamer NPs together achieved the down-regulation of TG in vivo and in vitro. Therefore, our findings provided a novel thought in treating these diseases associated with lipid deposition, that is, nanoparticles modified by specific structure exhibit a superior TG removal.