Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment

Abstract

Abstract Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. The BRD4 inhibitor JQ1 has powerful anti-fibrosis properties, its clinical application is extremely limited due to its side effects. There is still an unmet need for effective, safe and low-cost treatment. Here, a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) is presented, which is assembled by platelet membranes and red blood cell membranes to deliver JQ1 for treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of erythrocyte membrane can increase the long-term circulation ability of the nano drug-loaded system and can be further engineered to increase fluidity. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release to achieve excellent anti-fibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of novel fusion membrane biomimetic nanodrug carrier system can effectively reduce fibroblast activation, reduce collagen secretion, and improve cardiac fibrosis. In addition, it can greatly reduce the toxic and side effects of long-term JQ1 treatment on the liver, kidney and intestinal tract. These results suggest that the integration of native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system has great potential value in the treatment of cardiac fibrosis and the prevention of drug side effects.