Assessment of adsorption behavior of 5-fluorouracil and pyrazinamide on carbon nitride and folic acid-conjugated carbon nitride nanosheets for targeting drug delivery

Abstract

In this study, in order to improve the therapeutic efficacy and enhancing targeted delivery of anticancer drugs, a kind of potential carrier based on conjugated with folic acid (FA) is designed. For this reason, the interactions of 5fluorouracil (5Fu) and pyrazinamide (PZA) anticancer drugs with pristine carbon nitride (CN) and its conjugated form with folic acid (FA-CN) using density functional theory (DFT) calculations and molecular dynamics (MD) simulation are investigated. The obtained results demonstrate that the functionalization of nanocarrier with FA not only improves the therapeutic efficacy but also causes the adsorption of the drugs to be stronger. Also, it found that the adsorption of 5Fu on the CN and FA-CN is stronger than PZA. The DFT-D performance in this work indicates that the dispersion correction has a strong effect on improving the obtained results. According to DFT-D calculations, the adsorption energy of 5Fu on the pristine nanocarrier is about −10 kJ/mol less than PZA. After the functionalization of nanocarrier, the adsorption energies about 20% become stronger. The closed-shell (non-covalent) interactions between the drugs and the nanosheets using the quantum theory of atoms in molecule (QTAIM) calculations are confirmed. Charge transfer calculation by employing the NBO method reveals that the nanosheets act as donors, and drugs act as acceptors. Furthermore, the obtained results from MD simulation have a good agreement with DFT results and showed similar trends. Generally, the results reveal that CN and FA-CN nanosheets can be used as suitable platforms for the delivery of anticancer drugs.