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Micropatterned Magneto-Rheological Elastomers to Drive Changes in Cardiomyocyte Alignment
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Matrix Metalloproteinase-9-Responsive Lipid-Core Micelles for Proof-of-Concept Enzyme-Triggered Cardiomyocyte

Wai-Houng Chou1, Jafet Ortiz-Quintero2,3, Sergio Bedoya4

  • 1Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad Católica del Norte, 1240000, Antofagasta, Chile.

AAPS Pharmscitech
|June 8, 2026
PubMed
Summary

Researchers created enzyme-responsive nanoparticles for cardiovascular diseases (CVDs). These lipid-core micelles (LCMs) target heart cells and respond to matrix metalloproteinase-9 (MMP-9), showing potential for targeted drug delivery in CVD treatment.

Keywords:
MMP-9cardiomyocyte associationcardiovascular drug deliveryenzyme-responsive nanocarrierslipid-core micelles

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cardiovascular Research

Background:

  • Cardiovascular diseases (CVDs) are a leading cause of death globally.
  • Increased matrix metalloproteinase-9 (MMP-9) activity is linked to cardiac remodeling and inflammation in CVDs.
  • Targeted delivery systems are needed to address localized pathological processes in the heart.

Purpose of the Study:

  • To develop and evaluate enzyme-responsive lipid-core micelles (LCMs) for targeting cardiomyocytes.
  • To incorporate a peptide with a cardiomyocyte-targeting sequence (PCM-1) and an MMP-9 cleavable linker.
  • To demonstrate proof-of-concept for an enzyme-responsive nanoparticle platform for CVDs.

Main Methods:

  • Functionalization of LCMs with a peptide containing PCM-1 and an MMP-9 cleavable linker.
  • Preparation of nanoparticles using low-energy hot emulsification.
  • Characterization of nanoparticle size, charge, and cargo entrapment efficiency.
  • In vitro assessment of enzymatic accessibility, cleavage kinetics, and cardiomyocyte association.

Main Results:

  • Developed spherical, monodisperse LCMs (12-16 nm) with high rhodamine entrapment efficiency (>80%).
  • Surface-displayed peptide showed functionally relevant MMP-9 responsiveness, albeit with reduced kinetics.
  • LCMs exhibited enhanced cardiomyocyte association compared to non-functionalized particles, indicating preserved targeting.

Conclusions:

  • Mechanistic proof-of-concept for MMP-9 responsive LCMs that modulate targeting and release behavior.
  • Enzyme-triggered transitions alter nanoparticle behavior and cargo release.
  • Supports further investigation of enzyme-responsive targeting strategies for cardiovascular diseases.