CTF-1 triazine framework as a drug delivery surface for the anticancer drugs carmustine and temozolomide: a DFT study

Abstract

Traditional macroscopic drug administration systems suffer from poor adsorption and poor bioavailability of drugs; therefore, targeted drug administration systems are used for the delivery of drugs to reduce the dosage and minimize the adverse effects of the drugs on normal cells. 2D materials are studied for their ability to enhance adsorption and bioavailability as their periodic cavities provide ideal sites for drugs to bind effectively at target locations, thereby improving their therapeutic potential. In this context, the CTF-1 porous covalent triazine framework was studied for the delivery of anti-cancer drugs carmustine (BCNU) and temozolomide (TMZ). In the studied complexes, the adsorption energies in the gas phase, including BSSE corrections, indicated a higher interaction for TMZ@CTF-1 (−19.89 kcal mol⁻¹) than for BCNU@CTF-1 (−13.51 kcal mol⁻¹). The nature of the interactions was studied through NCI and QTAIM analyses, which revealed that van der Waals interactions played a key role in the stability of the complexes. Additionally, the stability of the complexes was verified by the symmetry-adapted perturbation theory (SAPT0), which indicated that dispersion energy is the major contributing factor in the stability of both complexes. FMO analysis revealed that the HOMO–LUMO gap of the TMZ@CTF-1 (7.60 eV) complex was slightly reduced compared to that of the bare CTF-1 surface (7.72 eV), indicating a change in the electronic properties upon drug adsorption. NBO and EDD analyses revealed that a higher charge was transferred in the TMZ@CTF-1 complex. Furthermore, the dipole moment increased after the adsorption of the drugs, which improved the solubility of the drugs in the biological system. This study reveals that the off-loading of drugs is facilitated at lower pH values, which is an advantage because cancerous cells have a lower pH than normal cells. We strongly believe that this study will guide experimentalists in exploring new surfaces, such as covalent triazine frameworks, for drug delivery.