Cavitands based nanocapsule as smart and highly effective vehicle for 5-fluorouracil anti-cancer drug delivery: DFT insights

The nanomaterials have been widely investigated as drug delivery system for a variety of anticancer drugs to limit their adverse effects while transporting to the target site. In the current study, we report the cavitand-based nanocapsules as a drug delivery vehicle for nitrosourea (NU) and fluorouracil (FU) anti-cancer drugs. FU and NU drugs interact with the nanocapsules with the interaction energies in gas phase (solvent) −24.78 kcal/mol (–22.39 kcal/mol) and −21.58 kcal/mol (-20.45 kcal/mol), respectively. The results of Quantum theory of atoms in molecules (QTAIM) and noncovalent index (NCI) analyses indicate that the FU@Capsule and NU@Capsule complexes are mainly stabilized through hydrogen bonding and van der Waals interactions. Electron density difference (EDD) and natural bond order (NBO) analyses reveal that significant amount of charge is transferred from the nanocapsule to drug molecules. Frontier molecular orbital (FMO) analysis also reveals slight reduction in the energy gap. AIMDS analysis shows that cavitand capsules can efficiently carry the anti-cancerous drug to their target site without distorting complexes. The dipole moments and pH effect are studied to understand the drug release mechanism of considered anticancer drugs. The decrease in adsorption energy and increase in interaction distances indicate that anticancer drugs can easily be off-loaded from the carrier (nanocapsule) at the target site due to the low pH of cancerous cells compared to the normal cells. Therefore, cavitand nanocapsule can be employed as an excellent drug delivery carrier in smart targeted drug delivery.