Dinâmica molecular de nanohorns de carbono (NHC): potenciais agentes carreadores de complexos antitumorais de Pt(II)

Abstract

Chemotherapy involving Pt(II)-based drugs, such as cisplatin, has demonstrated effective results against cancer cells, despite the severe side effects due to the high toxicity associated with the low selectivity of these antitumor agents. A potential alternative to overcome or decrease the side effects is to use drug delivery systems, which can provide protection against degradation, carry high doses of the anticancer drug and promote its slow and targeted release to the tumor sites. Herein, by using the molecular dynamics method, the purpose of this work was to investigate and characterize the dynamical behavior of the inclusion complexes cddp@CNH, formed by the encapsulated cisplatin (cddp) inside carbon nanohorns (CNH) models, in aqueous solution. In relation to these nanocarriers based on carbon atoms, it was evaluated the potentiality of both pristine models with different opening cone angles, and oxidized (CNHox) and reduced (CNHh) models, which were distinguished in terms of the size of the functionalized nanowindows generated by oxidation and reduction stages. The results indicated the presence of up to 36 water molecules inside the empty CNH cavity, depending on the cone angle and the presence of the cddp. Some of these solvent molecules are expelled out to the bulky upon cddp inclusion, although more than 10 molecules remain confined. In contrast, the complexes including CNHox and CNHh prototypes carried up to 17 and 15 solvent molecules, respectively. The increase in the degree of oxidation was also relevant for the expansion of the solvent accessible surface area, and consequently, for the hydrophobicity reduction of CNH. The effect of cddp release was made impossible by the obstruction of functionalized nanowindows. Moreover, as reported in experimental studies, the calculated binding free energy (ΔbG) pointed out that the inclusion complexes formation between CNH structures and up to two cddp molecules was thermodynamically favorable in aqueous media, which suggests the potential of this carbon nanostructures as drug carriers. While for the complexes with the most likely pristine CNH the average ΔbG was -35 and -79 kcal mol⁻¹ for inclusion of one and two cddp, respectively, for the complexes with CNHox and CNHh the referred values of the average ΔbG were -47 e -77 kcal mol⁻¹ and -40 e -74 kcal mol⁻¹ respectively, with most of the complex stability coming from the van der Waals contributions.