Molecular Dynamics Simulations of the pH-Dependent Adsorption of Doxorubicin on Carbon Quantum Dots

In this work, the combined effect of the amount of oxygen-containing groups on the carbon quantum dot (CQD) surface and the pH level on the interaction mechanism between an anticancer drug and a carrier has been studied. Molecular dynamics simulations of loading and release of doxorubicin (DOX) molecules on the CQD surface at pH = 7.4 and pH = 5 were carried out, followed by binding free energy calculations with steered molecular dynamics. The results indicate that the CQDs-DOX interaction strength increases with the surface coverage and pH, as well as that the electrostatic interaction between DOX and CQDs plays a significant role in the drug-loading process. This effect was partly attributed to the different surface orientations of the DOX molecular fragments. The obtained results provide the microscopic picture of DOX loading and release on/from the CQDs, which may be critical for the development of advanced CQD-based targeted drug delivery systems.