H2O2-responsive lovastatin nanohybrids based on auto-fluorescent perylene diimide reverse nonalcoholic fatty liver disease
Nonalcoholic fatty liver disease (NAFLD) is a typical metabolic disease caused by excessive accumulation of lipid in the liver. Lovastatin (Lov) is a representative of a classic lipid-lowering drug, but the drug has a lack of targeting, and the toxic and side effects are serious. Reactive oxygen species (ROS), which can lead to a “second strike” of NAFLD, eventually lead to cirrhosis and hepatic cancer. Therefore, a H2O2-responsive and self-fluorescence prodrug-nanosystem (PBI-Lov) has successfully been constructed. While consuming ROS and leading to breaking of the oxalate bond, it will result in the release of lovastatin. Negatively charged phosphatidylserine (PS) was coated on PBI-Lov to prepare PS-PBI-Lov nanoparticles. The uptake of PS-PBI-Lov nanoparticles could be increased both in HepG2 cells and RAW264 7 cells. Most importantly, these fluorescence nanoparticles realized rapid, real-time and high-precision detection in tetracycline mice. PS-PBI-Lov nanoparticles effectively targeted the liver, and decreased both lipid accumulation and vacuole structures in the liver, reducing the degree of fibrosis, and effectively reversing the NAFLD.