Nashrieh Shimi va Mohandesi Shimi Iran

Nashrieh Shimi va Mohandesi Shimi Iran

Graphene Oxide Nanosheets as Bortezomib Drug Carriers in a Targeted Drug Delivery System: A Novel Approach for Cancer Therapy

Document Type : Research Article

Authors
Hooriye Yahyaei
Amir Reza Saeni
Department of Chemistry, Zanjan Branch, Islamic Azad University, Zanjan, I.R. IRAN
Abstract
This study, for the first time, investigates the interaction between the anticancer drug bortezomib and graphene oxide nanoparticles using quantum mechanical calculations employing density functional theory and NBO calculations at the B3LYP/6-311+G* level of theory, as well as molecular mechanics simulations using the Monte Carlo method with AMBER, OPLS, CHARMM (Bio), and MM+ force fields over a range of temperatures (298-316 K) in water solvent. Calculations have shown that hydroxyl and epoxy groups in graphene oxide form hydrogen bonds with the N-H group of the bortezomib molecule, while the carboxyl group at the edges of the graphene oxide sheet creates a negative surface charge. Therefore, graphene oxide is well dispersed in water and other polar solvents, and this amphiphilic structure, when faced with the bortezomib drug, introduces it as a suitable carrier. This is also observed in molecular docking simulations and molecular dynamics simulations through the establishment of precise hydrogen bonds and hydrophobic π bonds in this drug system; which, due to intramolecular hydrogen bonds of bortezomib with graphene oxide and hydrophobic bonds, provides intermolecular stabilization and stability of this drug system with the surrounding environment. According to NBO results, which are based on π-π interactions of graphene oxide and bortezomib, van der Waals, ionic, and hydrogen bonding interactions occur due to the presence of a large number of oxygen-containing groups, which has a significant impact on the stabilization of the anticancer drug bortezomib. Also, evaluations of the molecular electrostatic potential and molecular charges by examining the electrostatic interactions of this drug system in terms of electronegativity, desirability, and BTZ-GO stability have shown results consistent with NBO results. Monte Carlo calculations also show that the results extracted from the Amber force field are consistent with the results of quantum mechanics.
Keywords
Bortezomib
Nano graphene oxide
Natural bond orbitals (NBO)
Molecular electrostatic potential(MEP)
Mulliken atomic charges
Molecular docking(MDs)

Subjects

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