Describing the adsorption of doxorubicin on a PAMAM dendrimer by ab initio calculations†

Abstract

One of the cancer treatment methods is the use of doxorubicin as a chemotherapy drug. Despite its effectiveness, it has low specificity and high toxicity, thus affecting healthy cells in the body. One approach to reducing toxicity to healthy cells is the delivery of the active compound by a nanoparticulate system. The proposed doxorubicin transport system by polyamidoamine (PAMAM) dendrimer molecules was carried out experimentally, but the mechanism involved in this interaction has not yet been demonstrated. In this contribution, the interactions that occur in a nanoparticulate system with potential for a controlled drug release were described using density functional theory, as implemented in the SIESTA code. The delivery system is formed by a PAMAM dendritic molecule, the drug doxorubicin and two targeting molecules, namely folic acid and cis-aconitic anhydride. The results show that there is a hydrogen bonding interaction between PAMAM and doxorubicin, and the influence of targeting molecules is promising. An increase in the stability was observed when the cis-aconitic anhydride interacts with PAMAM. For all the configurations tested, the presence of a doxorubicin molecule changes the electronic properties of the PAMAM dendrimer, showing that the adsorption occurs for all the systems proposed.