Genetically Engineered Biomimetic ATP-Responsive Nanozyme for the Treatment of Cardiac Fibrosis

The study introduces a novel therapeutic approach for cardiac fibrosis using genetically engineered biomimetic ATP-responsive nanozymes, specifically FM@zif-90/Ce/siR NPs. These nanozymes target activated cardiac fibroblasts and are designed to reduce myofibroblast accumulation and fibrotic tissue formation, while restoring cardiac function. The nanoparticles, which combine CeO2 and siCTGF, demonstrate potent antioxidant and anti-inflammatory properties, effectively reducing reactive oxygen species (ROS) and pro-inflammatory cytokines. In a mouse model, these NPs decreased collagen deposition and fibroblast activation, leading to improved cardiac function. The study highlights the nanozymes' stability, high siRNA loading efficiency, and excellent hemocompatibility and biocompatibility, with a hemolysis rate below 5% and a cell survival rate of approximately 85%. The findings suggest that FM@zif-90/Ce/siR NPs could be a promising targeted therapeutic approach for treating cardiac fibrosis, with a favorable biosafety profile and potential for clinical translation.