Folic acid functionalized carbon nanotubes as pH controlled carriers of fluorouracil: Molecular dynamics simulations

Abstract

This study deals with molecular dynamics simulations of the folic acid (FA) functionalized carbon nanotube (CNT) as a pH-responsive carrier of fluorouracil (5-FU) drug. We chose FA as a targeting agent, as the folate receptor is considerably upregulated by a broad spectrum of cancer cells. Thus, it may facilitate the targeted delivery of chemotherapeutic agents. The results showed that the FA does not affect the loading capacity of CNT at neutral pH so both CNT and CNTFA can load 51 drug molecules. Unmodified CNT behaves in the same manner at different pH conditions, and so cannot be used as a pH-selective nanocarrier. However, the maximum loading capacity of CNTFA is decreased to 45 by decreasing the environmental pH. The molecular mechanics Poisson-Boltzmann surface area analysis showed that the hydrophobic and π-π stacking interactions are the main forces behind the complex stability. The least value of △Gbind belongs to the CNTFA:5-FU at low pH, which is favorable for drug release from a thermochemical viewpoint. The lowest and highest values of diffusion coefficients are those of CNTFA:5-FU at neutral and low pH, respectively. This means that CNTFA holds the drug molecules tightly at physiological pH, but releases them at low pH environments. Also, the reduction of the number of hydrogen bonds between CNTFA and 5-FU molecules as well as a decrease in height of the radial distribution function profile at low pH propose the CNTFA as a pH-sensitive nanocarrier for 5-FU. The simulation results show the important effect of the FA on the controlled release of 5-FU from CNT, which is suitable for targeted drug delivery applications.