Computational exploration of anticancer drug adsorption on a porous organic nanocage: Insights from density functional theory for targeted nanocarrier design

Abstract

Abstract Designing efficient nanocarriers for targeted cancer therapy requires a deep understanding of drug–nanomaterial interactions at the molecular level. In this study, the adsorption behavior of four clinically relevant anticancer drugs, 6-mercaptopurine (6-MP), hydroxyurea (HU), chlormethine (CM), and 5-fluorouracil (5-FU), on a CC1 nanocage was systematically investigated using density functional theory (DFT). Geometry optimizations and thermodynamic analyses were performed at the ωB97XD/6-31G(d, p) level, while optical properties were assessed through time-dependent DFT (TD-DFT) calculations at the B3LYP/6-31G(d, p) level. The computed adsorption energies and electronic descriptors revealed that all drug–nanocage interactions are spontaneous and exothermic in an aqueous medium, with 5-FU exhibiting the strongest binding (− 8.68 kcal/mol). TD-DFT spectra displayed redshifts in absorption peaks after adsorption, signifying charge transfer between the drugs and the CC1 framework. Moreover, topological (QTAIM) and Non-Covalent Interaction (NCI) analyses confirmed that van der Waals forces primarily stabilize the complexes. The short recovery times predicted for the drug-loaded nanocage suggest efficient release kinetics under physiological conditions. Overall, this theoretical study provides a molecular-level perspective on CC1 nanocage–drug interactions, offering useful insights for the rational design of carbon-based nanocarriers in targeted anticancer drug delivery.