Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation

The recent advances in nanotechnology are revolutionizing preventive and therapeutic approaches to treating cardiovascular diseases. Controlling the extracellular matrix metalloproteinase (MMP) activation and expression in the failing human left ventricular myocardium represents a significant therapeutic target for heart disease. In this study, we used molecularly imprinting polymers (MIPs) to restore the correct balance between MMPs and their tissue inhibitors (TIMPs), and explored the potential of this technique exhaustively through chemical synthesis, physicochemical and biological characterizations, and computational chemistry methods. By molecular dynamics simulations based on classical force fields, we simulated the early stages of the imprinting process in solution disclosing the pivotal interaction established between the monomers and the MMP9 protein template. The average interaction energies of methacrylic acid (MAA) and poly (ethylene glycol) ethyl ether methacrylate (PEG) units were in the ranges 17-22 and 30-37 kcal/mol, respectively. At low coverage, the PEG monomers seemed firmly anchored to the protein surface and were not displaced by water, while only about 20% of MAA was replaced by water. The synthesis of MIPs was successfully with a monomer conversion higher than 99% and the production of spherical particles with average diameter of 344 +/- 33 nm. HPLC analysis showed a specific recognition factor of MMP9 on MIPs of about 1.3. FT-IR Chemical Imaging confirmed the mechanisms necessary to generate a selective memory of the MIPs towards the enzyme. HPLC results indicated that the rebound amount of both TIMP1 and MMP2 to MIPs is lower than that of the template, showing a selectivity factor of 2.1 and 2.3, respectively. Preliminary tests on the effect of MIPs on H9C2 cells revealed that this treatment has no cytotoxic effects.

Automated summary

The recent advances in nanotechnology have revolutionized the prevention and treatment of cardiovascular diseases. This study utilizes molecularly imprinting polymers (MIPs) to restore the balance of MMPs and TIMPs in the failing human left ventricular myocardium. The research explores the potential of this technique through various methods and successfully synthesizes MIPs with high selectivity towards MMP9.