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

This study deals with molecular dynamics simulations of the folic acid (FA) functionalized carbon nan-otube (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 facil-itate 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 p-p stacking interactions are the main forces behind the complex stability. The least value of AGbind belongs to the CNTFA:5-FU at low pH, which is favorable for drug release from a ther-mochemical 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 physiolog-ical 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 pro-file 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.(c) 2023 Published by Elsevier B.V.

Automated summary

This study investigates the performance of folic acid-functionalized carbon nanotubes (CNT) as a pH-responsive carrier for fluorouracil (5-FU) drug through molecular dynamics simulations. The results demonstrate that folic acid does not affect the loading capacity of CNT at neutral pH, but it decreases at lower pH. The simulations suggest that folic acid plays an important role in the controlled release of 5-FU from CNT, making it suitable for targeted drug delivery applications.