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

Villano, Anthea; Barcaro, Giovanni; Monti, Susanna; Barbani, Niccoletta; Rizzo, Antonio; Rossin, Daniela; Rastaldo, Raffaella; Giachino, Claudia; Cristallini, Caterina

doi:10.3390/biomedicines10092070

Open AccessArticle

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

by

Anthea Villano

¹,

Giovanni Barcaro

¹

,

Susanna Monti

²

,

Niccoletta Barbani

^1,3,

Antonio Rizzo

¹

,

Daniela Rossin

⁴

,

Raffaella Rastaldo

⁴

,

Claudia Giachino

^4,†

and

Caterina Cristallini

^1,3,*,†

¹

CNR-IPCF, National Research Council—Institute for Chemical and Physical Processes, Area della Ricerca, Via Moruzzi 1, I-56124 Pisa, Italy

²

CNR-ICCOM, National Research Council—Institute of Chemistry of Organometallic Compounds, Area della Ricerca, Via Moruzzi 1, I-56124 Pisa, Italy

³

Department of Civil and Industrial Engineering, University of Pisa, I-56122 Pisa, Italy

⁴

Department of Clinical and Biological Sciences, University of Turin, I-10043 Orbassano, Italy

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to the work.

Biomedicines 2022, 10(9), 2070; https://doi.org/10.3390/biomedicines10092070

Submission received: 24 June 2022 / Revised: 14 August 2022 / Accepted: 20 August 2022 / Published: 24 August 2022

(This article belongs to the Special Issue Advances in Nanomaterials for Drug Delivery)

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Abstract

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.

Keywords: molecularly imprinted nanoparticles; nanomedicine; therapeutic target; metalloproteinase control; left ventricular remodeling; molecular dynamics; FT-IR Chemical Imaging

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MDPI and ACS Style

Villano, A.; Barcaro, G.; Monti, S.; Barbani, N.; Rizzo, A.; Rossin, D.; Rastaldo, R.; Giachino, C.; Cristallini, C. Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation. Biomedicines 2022, 10, 2070. https://doi.org/10.3390/biomedicines10092070

AMA Style

Villano A, Barcaro G, Monti S, Barbani N, Rizzo A, Rossin D, Rastaldo R, Giachino C, Cristallini C. Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation. Biomedicines. 2022; 10(9):2070. https://doi.org/10.3390/biomedicines10092070

Chicago/Turabian Style

Villano, Anthea, Giovanni Barcaro, Susanna Monti, Niccoletta Barbani, Antonio Rizzo, Daniela Rossin, Raffaella Rastaldo, Claudia Giachino, and Caterina Cristallini. 2022. "Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation" Biomedicines 10, no. 9: 2070. https://doi.org/10.3390/biomedicines10092070

APA Style

Villano, A., Barcaro, G., Monti, S., Barbani, N., Rizzo, A., Rossin, D., Rastaldo, R., Giachino, C., & Cristallini, C. (2022). Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation. Biomedicines, 10(9), 2070. https://doi.org/10.3390/biomedicines10092070

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

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