Cardiac homing peptide-decorated epigallocatechin gallate-loaded poly(lactic-co-glycolic acid) nanoparticles alleviate acute myocardial infarction.

Abstract

Epigallocatechin gallate (EGCG) exerts cardioprotective effects on acute myocardial infarction through multiple pathways. However, the clinical application of EGCG is limited because of its instability under physiological conditions and low bioavailability. In this study, poly(lactic-co-glycolic acid) was used as a drug carrier to prepare EGCG nanoparticles (NPs), then an EGCG targeting drug delivery system was designed by modifying with cardiac homing peptide. We constructed a preparation route combining the double-emulsion solvent evaporation method and the carbodiimide method. By optimizing the preparation process, the particle size of the EGCG NP was reduced, and the dispersibility was improved. In addition, the established preparation procedure uses safe and low-toxicity reagents, requires no strict temperature control or specialized instrumentation, and therefore significantly reduces the technical difficulty of large-scale industrial production. EGCG-poly(lactic-co-glycolic acid)-cardiac homing peptide had myocardial targeting and good safety in the 3‑(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2H‑tetrazolium bromide (MTT) cytotoxicity test, and alleviated acute myocardial infarction by regulating apoptosis-related protein expression in a dose-dependent manner. Compared with EGCG monomer, EGCG-poly(lactic-co-glycolic acid)-cardiac homing peptide achieved a better therapeutic effect. This study provides a new strategy for promoting the application of EGCG in the clinical treatment of acute myocardial infarction. SIGNIFICANCE STATEMENT: This study develops cardiac homing peptide-modified poly(lactic-co-glycolic acid) nanoparticles to enable targeted delivery of epigallocatechin gallate for acute myocardial infarction therapy. By overcoming the inherent instability and poor bioavailability of epigallocatechin gallate, this scalable nanoplatform achieves superior cardioprotection through regulated apoptosis and exhibits excellent safety in the MTT cytotoxicity test. These findings establish a clinically translatable strategy for targeted drug delivery in the treatment of cardiovascular disease.