A strategy toward therapeutic improvement of electric field-sensitive gemcitabine prodrugs in 2D metal–organic frameworks in view of their structure and interactions

Abstract

• The interaction energy of the drug-polymer with MON stronger than the free drug. • Higher value of external electric field will help in better absorption. • A 10% defect leads to a 50% increase in the total interaction energies of the carrier with the PPY-GEM molecules. Gemcitabine, among other chemotherapeutic agents, helps to save many lives in fighting cancers of various types. Nevertheless, many side effects arise from the high dosage required for effective treatment. Nanotechnology-based drug delivery systems (DDSs) are among the newly proposed strategies proposed to send chemotherapeutic agents directly to tumor cells and reduce their hazardous concentrations in healthy tissues. In this paper, through density functional theory (DFT) calculations and molecular dynamics (MD) simulations, a new DDS is designed in which gemcitabine is conjugated to an electric field-responsive polymer called polypyrrole and loaded on a metal–organic nanosheet (MON). DFT calculations reveal that covalent bonding between the drug and polymer has a limited impact on the chemical properties of the drug. On the other hand, the MD simulation suggested that the adsorption of the drug on the CuBDC nanoparticle is highly improved by conjunction with polymer. The interaction energy of the drug-polymer complex with MON is approximately 138 kJ/mol stronger than the corresponding value for the free drug. Furthermore, implementation of a lower magnitude of the external electric field may reduce the adsorption interaction energies, while a higher value will help in better absorption.