Collagen-Like Peptide Nanoparticles for Methylglyoxal Trapping

Abstract

Cardiovascular diseases (CVDs) remain the leading global cause of death, with myocardial infarction (MI) a major contributor. Following MI, toxic metabolites like methylglyoxal (MG), a glycolysis byproduct, accumulates and increases formation of advanced glycation end-products (AGEs), inducing protein crosslinking, tissue stiffening, and signaling dysregulation, ultimately contributing to cardiac dysfunction. Collagen-like peptides (CLPs) offer a versatile strategy for cardiac repair. Here, we designed CLPs containing arginine motifs optimized for MG scavenging. Spectroscopy and in vitro studies confirmed collagen-like behaviour and MG-trapping activity without exogenous molecules. To enhance delivery, we developed self-assembled nanoparticles (NPs) from Fmoc-tyrosine and Fmoc-tryptophan, crosslinked via photopolymerization using Irgacure-2959. These NPs showed stability under purification, processing, and storage. Encapsulation efficiency (EE) studies better efficiency in phosphate buffer, achieving EE up to 72% EE (83.9 ug peptide/ 0.31 mg NPs). Together, this highlights the potential of our MG-trapping peptide delivered via NPs as a potential therapeutic for post-MI cardiac repair.