Precisely and Efficiently Enzyme Response Microspheres with Immune Removal Escape Loaded with MCC950 Ameliorate Cardiac Dysfunction in Acute Myocardial Infarction

Abstract

Although the percutaneous coronary intervention (PCI)treatment can improve the survival rate of acute myocardial infarction (AMI) patients, the early granulocytes response within 6 hours can induce second injuries during the reperfusion process. The new drug delivery system MMP9 hydrolytic microspheres (NMM) with negatively charged surface was designed out and MCC950 (MCC) was loaded into NMM (NMM-M), MCC is the inhibitor of nucleotide binding oligomerization domain (NOD)-like receptor, pyrin containing domain 3 (NLRP3)-inflammasome which is the key promoter of granulocytes-induced injury. NMM-M could effectively escape the phagocytosis of immune phagocytes in the blood, and target the ischemic region based on the electrostatic attraction and the attraction of enzyme to substrate, and sudden release the loaded MCC within 2 hours. The released MCC can inhibit the NLRP3-inflammasome activity, and then further inhibit the secretion of inflammatory factors in granulocytes which are the main factors of early inflammatory damage, and improving cardiac function, realizing the goal of pre-treatment. Therefore, NMM may be a new delivery system, which can provide the accurately, sufficient and rapidly drug deliver, and MCC may be a novel candidate drug in AMI treatment, which may be hopeful in the future.