<p>This study examined the adsorption of the mechlorethamine (ME) anti-cancer drug loaded upon Mg₁₂O₁₂ nanocage using DFT: B3LYP (6-31G* and 6-311G** basis set) and B3PW91 (6-31G* basis set) calculations. To clarify the electronic, thermochemical, and structural properties of drug (ME) complexes with Mg₁₂O₁₂ nanocages, DFT calculations were combined with the Quantum Theory of Atoms in Molecules (QTAIM) study. NBO analysis revealed that the maximum stability energy of the electronic transfer of ME into Mg₁₂O₁₂ nanocavities originated from the LP(1)N27 to LP*(1)Mg5 transition with an E2 value of 17.63 kcal mol. Further, the maximum stability energy value obtained from Mg₁₂O₁₂ nanocages to the drug ME was owing to the electronic shift from LP*(1) Mg 5 to σ*C 31—H 41 orbitals compared to the drug/nanotube complex with E2 = 0.81 kcal.mol-1. Based on the QTAIM results, -G(r)/V(r) value ​​for the interaction between the H41 atom of the ME drug and the O13 atom of the nanocage [(C31-H41 (ME)…O13 (nanocage)] was about 0.37, indicating the covalent nature of the interaction. In the UV–Vis spectrum, the wavelength shift from 198 to 258 nm with the adsorption of the drug on the nanosorbent revealed a bathochromic change (red shift). The values ​​of ∇2ρ and ρ are associated with hydrogen bonds between atoms H41 and O13 (∇2ρ = 0.0602; ρ = 0.0208) as well as atoms O15 and H43 ∇2ρ = 0.0525; ρ = 0.0179). Thus, the interactions mentioned in this series are related to hydrogen bonds. Accordingly, based on the results obtained, Mg₁₂O₁₂ nanoclusters can be used as a promising carrier for ME drug delivery.</p> Graphical Abstract <p></p>