Mechanistic insights into melphalan release from TM-doped boron nitride nanosheets: a comprehensive DFT investigation

Abstract Targeted delivery of anticancer pharmacological agents significantly reduces adverse secondary effects and allows for localized release of therapeutics in proximity to neoplastic cells. Density Functional Theory (DFT) computations were utilized to explore both pristine and transition metal (Co, Cu, Fe, Ni, and Au) doped boron nitride nanosheets (BNNSs) as prospective nanocarriers for the anticancer pharmaceutical melphalan (Mln). The computed adsorption energies span from −0.32 to −0.89 eV for pristine, Co-, Ni-, and Au-doped BNNSs, signifying physisorption primarily governed by weak interactions, whereas more substantial binding energies of −1.21 and −1.22 eV are recorded for Cu- and Fe-doped BNNSs, corroborating a chemisorptive mechanism. All adsorption phenomena are exothermic and thermodynamically advantageous. The charge transfer from the BNNS surface to Mln fluctuates between 0.02 and 0.23 |e|, accompanied by significant alterations in the HOMO–LUMO gap, particularly within the Au- and Fe-doped configurations. Ni-, Co-, and Au-doped BNNSs display moderate adsorption intensity and reduced estimated recovery durations, indicating expedited drug release, whereas Fe-doped BNNSs demonstrate enhanced binding appropriate for regulated drug retention. These findings elucidate that transition metal doping facilitates adjustable interaction strength within BNNS-based drug delivery systems. Collectively, this theoretical investigation underscores the potential of TM-doped BNNSs as effective nanocarriers for Melphalan, proposing pH-responsive release and recovery duration as innovative design parameters for the future development of anticancer drug delivery systems.