Nb₂C-based MXenes for controlled cyclophosphamide delivery: role of surface functionalization and sulfur doping

A systematic first-principles study was performed to explore the pristine Nb₂C, Nb₂CO₂, and S-doped Nb₂CO₂ MXenes as potential nanocarriers for cyclophosphamide (CYP) drug delivery in breast cancer therapy. Density functional theory calculations were employed to examine the structural stability, electronic properties, adsorption behaviour and solvation effects of all systems. Cohesive energy calculations and ab initio molecular dynamics simulations confirmed the structural and thermal stability of all nanocarriers at 298 K. Electronic structure analysis revealed that the metallic nature of the MXenes is preserved after functionalization, sulfur doping and drug adsorption. Adsorption studies showed that pristine Nb₂C exhibits strong interaction with CYP, with an adsorption energy of -1.02 eV, indicating chemisorption. In contrast, Nb₂CO₂ displayed relatively weak physisorption. Sulfur doping effectively modulates the adsorption strength, and the 4S-doped Nb₂CO₂ configuration exhibited -0.85 eV of adsorption energy with reduced charge transfer, suggesting a favourable balance between drug loading and release. Implicit solvation calculations showed that both isolated and drug-loaded systems are stable under aqueous conditions, with solvation energies of up to -0.36 and -0.74 eV, respectively. Recovery time analysis at physiological temperature (310 K) further confirms the suitability of these MXenes for drug release. Among all investigated nanocarriers, 4S-doped Nb₂CO₂ MXene is emerging as a candidate for CYP drug delivery applications.