Surface functionalization of boron nitride nanosheet with folic acid: Toward an enhancement in Doxorubicin anticancer drug loading performance.

Abstract Loading of the Doxorubicin (DOX) as an anticancer drug molecule on boron nitride (BN) nanosheets with different sizes, in the presence and absence of Folic Acid (FA) functional groups, are investigated using molecular dynamic simulations. The obtained results from these investigations revealed that the drug molecules are spontaneously adsorbed the carriers and form stable complexes. It is also shown that an increase the nanosheet leads to an enhancement in its capacity to adsorb the drugs. Furthermore, the conjugation of BN with the FA group not only improves the BN efficiency for the drug adsorption but also helps the drug-carrier complex to target the cancerous cells. Evaluation of interaction energies reveals that L-J interaction plays an essential role in the adsorption of the drug molecules on the BN. The radial distribution function (RDF) shows that the highest drug position probability is around 0.6 nm away from the BN surface. Atomic RDF analysis is in line with the interaction energy analysis and proved that π-π stacking contributes the most to this process. Hydrogen bond (HB) analysis also shows that, although limited, the columbic interaction can be helpful in the adsorption process. Moreover, the free energy (FE) surface is explored for a system containing a BN nanosheet, an FA group, and a DOX molecule through metadynamics simulations. The obtained results reveal that the lowest FE point located in coordinations d1 = 0.70 nm and d2 = 0.84 nm, and energetically reached −280.42 kJ/mol. It can be concluded from the FE calculations that while the FA is stuck on the substrate, DOX faces difficulty in the way it be adsorbed. In return, it will be hard for the molecule to be released from the BN surface through desorption processes in neutral pH because it faces an energy barrier with a height of ∼100 kJ/mol at 1.6 nm.