Abstract
Cisplatin (cddp)-based chemotherapy is one of the most effective therapeutic alternatives for breast cancer treatment, the most common form of cancer, despite the severe side effects related to the high toxicity and low selectivity of cddp. To circumvent these drawbacks, the encapsulation of cddp into oxidized carbon nanohorns (CNHoxs) has been shown as a promising formulation with biocompatibility and low toxicity. However, there is still a lack of studies regarding the behavior of this cddp@CNHox nanovector on the cell membranes. This study presents an in silico description of the interactions between cddp@CNHox and membrane models of cancer (C_memb) and normal (N_memb) cells referring to a typical human breast. The results revealed the interaction mechanism of the inclusion complex 3cddp@CNHox (three cddp molecules are included in the CNHox cavity) with these biomembranes, which is a multistep process including approach, landing, insertion, and penetration. The 3cddp@CNHox stability was monitored over time, and demonstrated the trapping of cddp molecules inside the CNHox cavity over all simulations. The van der Waals contribution played a primary role (∼74%) for the complex stability. Moreover, the binding free energy calculations indicated that the interaction of the 3cddp@CNHox complex with the C_memb model was slightly more favorable, on average, than with the N_memb model. Analysis of the hydrogen bonds (HBs) formed over simulations of 800 ns explains the selectivity for the C_memb model, since the total number of HBs established between the inclusion complex and the C_memb model was about three times greater than that with the N_memb model. By reinforcing the potentiality of oxidized CNHox as a nanovector of cddp, the results presented in this study may assist and drive new experimental studies with this nanomaterial, focusing on the development of less aggressive formulations for breast cancer treatment.
