Platelet-neutrophil hybrid membrane-coated gelatin nanoparticles for enhanced targeting ability and intelligent release in the treatment of non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is the major form of chronic liver disease in adults; however, there are no approved drugs for NASH. In this study, we designed the PNM-G-PV method, in which gelatin nanoparticles (G) are loaded with pioglitazone and vitamin E (G-PV) and then encapsulated by the surfaces of platelet-neutrophil hybrid membranes (PNM). Inherited from the natural source cells, the PNM show immune evading ability due to the surface marker comprising a number of "do not eat me" signals and has dual inflammatory enrichment capabilities due to specific surface adhesion molecules. By functionalizing the gelatin nanoparticle biomimetic surfaces, PNM-G can enhance the targeting to inflammatory sites and enrich liver tissue. The high expression of matrix metalloproteinase-9 (MMP-9) at the NASH site enables the gelatin nanoparticles to intelligently respond to degradation and then release vitamin E and pioglitazone for drug treatment. We performed an in vivo analysis of these nanoparticles to monitor changes in triacylglycerol metabolism in liver tissues and assessed the therapeutic efficacy of PNM-G-PV in a NASH rat model. The results showed that PNM-G-PV exhibited better therapeutic efficacy than therapies using G-PV or PV alone. This work explores a new biomedical use of PNM-G-PV and a promising NASH treatment protocol based on a new drug delivery system.