Investigation of metallacages for cisplatin encapsulation using Density Functional Theory (DFT)

Cancer is highly complex, including cross-talks between signalling pathways and multiple genes. Fortunately, successful anti-cancer drugs, such as cisplatin, are promising to treat cancer. Despite its clinical success, cisplatin presents several issues, including neurotoxicity, ototoxicity, nephrotoxicity and drug resistance. These limitations of the successful anti-cancer cisplatin can be overcome with the help of novel supramolecular drug delivery systems. This research aims to optimise novel supramolecular drug delivery systems – metallacage (M2L4}(M = metal, L = ligand) – that can be used to encapsulate cisplatin to protect it from metabolism. Specifically, we investigated the shape and stability of ten metallacages using different metals: Pt2+, Pd2+, Ni2+, Cu2+ and Au3+ using Density Functional Theory (DFT) methods to encapsulate one or two cisplatin molecules. Thus, we applied WebMo running PBE0 and Hartree Fock as theories, with LanL2DZ as a basis set. The results demonstrate that PBE0/LanL2DZ is the best method to describe the cages. The results show that Endo-N Ni2L4 and Endo-N Cu2L4 cages are the best option to encapsulate one and two cisplatin, while the least suitable system is Endo-C Pt2L4 and Endo-C Au2L4 for cisplatin encapsulation. Furthermore, endo-C cages are farther from ground state energy because of their higher energy than endo-N cages. Therefore, endo-N cages are superior to endo-C cages for the encapsulation of cisplatin.