Inorganic nanoparticles show promising properties that allow them to be efficiently used as drug carriers. The main limitation in this type of application is currently the drug loading capacity, which can be overcome with a proper functionalization of the nanoparticle surface. In this study, we present, for the first time, a computational approach based on metadynamics to estimate the binding free energy of the doxorubicin drug (DOX) to a functionalized TiO2 nanoparticle under different pH conditions. On a thermodynamic basis, we demonstrate the robustness of our approach to capture the overall mechanism behind the pH-triggered release of DOX due to environmental pH changes. Notably, binding free energy estimations align well with what is expected for a pH-sensitive drug delivery system. Based on our results, we envision the use of metadynamics as a promising computational tool for the rational design and in silico optimization of organic ligands with improved drug carrier properties.

Motta, S., Siani, P., Donadoni, E., Frigerio, G., Bonati, L., Di Valentin, C. (2023). Metadynamics simulations for the investigation of drug loading on functionalized inorganic nanoparticles. NANOSCALE, 15(17), 7909-7919 [10.1039/d3nr00397c].

Metadynamics simulations for the investigation of drug loading on functionalized inorganic nanoparticles

Motta, Stefano
Primo
;
Siani, Paulo
Secondo
;
Donadoni, Edoardo;Frigerio, Giulia;Bonati, Laura
Penultimo
;
Di Valentin, Cristiana
Ultimo
2023

Abstract

Inorganic nanoparticles show promising properties that allow them to be efficiently used as drug carriers. The main limitation in this type of application is currently the drug loading capacity, which can be overcome with a proper functionalization of the nanoparticle surface. In this study, we present, for the first time, a computational approach based on metadynamics to estimate the binding free energy of the doxorubicin drug (DOX) to a functionalized TiO2 nanoparticle under different pH conditions. On a thermodynamic basis, we demonstrate the robustness of our approach to capture the overall mechanism behind the pH-triggered release of DOX due to environmental pH changes. Notably, binding free energy estimations align well with what is expected for a pH-sensitive drug delivery system. Based on our results, we envision the use of metadynamics as a promising computational tool for the rational design and in silico optimization of organic ligands with improved drug carrier properties.
Articolo in rivista - Articolo scientifico
Metadynamics; DOX; nanoparticle; TiO2; Titanium Dioxide; drug loading
English
31-mar-2023
2023
15
17
7909
7919
none
Motta, S., Siani, P., Donadoni, E., Frigerio, G., Bonati, L., Di Valentin, C. (2023). Metadynamics simulations for the investigation of drug loading on functionalized inorganic nanoparticles. NANOSCALE, 15(17), 7909-7919 [10.1039/d3nr00397c].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/420665
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