Adaptive enzyme-responsive self-assembling multivalent apelin ligands for targeted myocardial infarction therapy

Area of Science:

• Cardiovascular Research
• Biomaterials Science
• Regenerative Medicine

Background:

• Myocardial infarction (MI) leads to microvascular dysfunction, worsening coronary obstruction and impairing ventricular function.
• The apelinergic system shows therapeutic potential for MI by improving vascular function and repairing ischemic myocardium.
• Limitations of natural apelin peptides and current analogs include short half-life, low receptor binding, and poor targeting.

Purpose of the Study:

• To develop an enzyme-responsive peptide that self-assembles at MI lesions for targeted apelin delivery.
• To enhance the efficacy of apelin-based therapies by overcoming limitations of existing analogs.

Main Methods:

• Utilized an enzyme-responsive peptide self-assembly technique.
• Engineered a peptide to respond to matrix metalloproteinases (MMPs) overexpressed in MI lesions.
• Developed a supramolecular multivalent peptide ligand (SAMP) through self-assembly.

Main Results:

• SAMP precisely presents the apelin motif at high MMP concentrations in MI lesions.
• Self-assembly prolongs apelin residence time and enhances receptor-ligand interaction via multivalency.
• SAMP significantly promoted angiogenesis, reduced cardiomyocyte apoptosis, and improved cardiac function post-ischemia.

Conclusions:

• The enzyme-responsive peptide self-assembly strategy offers precise and effective delivery of apelin to MI lesions.
• SAMP demonstrates significant therapeutic benefits for restoring coronary microvascular function and improving cardiac function after MI.
• This novel approach presents a promising therapeutic strategy for myocardial infarction treatment.