Therapeutic potential of C2N as targeted drug delivery system for fluorouracil and nitrosourea to treat cancer: a theoretical study

Conventional drug delivery systems suffer from poor absorption and poor bioavailability at the target site due to either very weak or very strong adsorption of drug on the carrier. Porous 2D nanostructures can offer better drug delivery system provided the system chosen has suitable cavity with heteroatoms for reasonable interaction with drug molecules. C2N is a surface of choice in this regard; therefore, potential of C2N surface as drug delivery system for nitrosourea and fluorouracil (drugs) is explored here. Both nitrosourea and fluorouracil interacted with the electron rich central cavity of C2N. Different structural and electronic parameters show that both drugs have good adsorption on C2N surface and thus can be carried to the target easily. Values of interaction and basis set superposition error (BSSE) corrected energies are slightly higher for nitrosourea@C2N as compared to fluorouracil@C2N. While all other properties such as non-covalent interaction (NCI), symmetry-adapted perturbation theory (SAPT0), quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO), electron density difference (EDD) and frontier molecular orbital (FMO) analyses illustrate that C2N is better carrier for nitrosourea than fluorouracil. The off-loading of drug is explored through molecular dynamics simulations which reveal that slightly elevated temperature can cause off-loading of the drug at the target cancer cell, which usually have temperature higher than the normal cells. MD simulations reveal that atomic interactions between the drugs and C2N are destabilized at higher temperatures. Comparison of the loading and off-loading mechanism with other surfaces reported in the literature reveal that C2N is a better carrier for these drugs. [GRAPHICS]