The PEGylated and non-PEGylated interaction of the anticancer drug 5-fluorouracil with paramagnetic Fe3O4 nanoparticles as drug carrier

Abstract

• The chemotherapy drug, 5-fluorouracil, is adsorbed to Fe 3 O 4 nanoparticles that act as a nanocarrier during targeted drug delivery. • Binding energy as a function of nanoparticle size is investigated. • Chemisorption, physisorption and hydrogen bonding is reported on. • Drug release, delivery and potential modifications at elevated temperatures are reported on. • The drug’s HOMO-LUMO and electrostatic potential are reported on. A simulation study is done on the anticancer drug, 5-fluorouracil, on PEGylated and non-PEGylated Fe 3 O 4 nanoparticles (NPs) to be employed as drug delivery vehicles. This is done for NP sizes varying from 1 to 6.9 nm and within a molecular dynamics (MD) study with a Monte Carlo simulated annealing scheme. Bonding modes are investigated with reference to chemisorption, physisorption and hydrogen bonding in the context of bond strength (binding energy) as a function of the 5-fluorouracil molecule’s loading on different sized NPs. Density functional theory (DFT) simulations are also performed to investigate the frontier molecular orbitals and molecular electrostatic potentials. This is done in the context of the interaction of the anticancer drug with DNA to explore if the use of this drug carrier may have the potential to alter the drug’s chemistry before delivery to the target site and therefore reduce its efficacy. Interactions with water molecules are also studied.