RESUMEN

Loading of the Doxorubicin (DOX) as an anticancer drug molecule on boron nitride (BN) nanosheets with different sizes, in the presence and absence of Folic Acid (FA) functional groups, are investigated using molecular dynamic simulations. The obtained results from these investigations revealed that the drug molecules are spontaneously adsorbed the carriers and form stable complexes. It is also shown that an increase the nanosheet leads to an enhancement in its capacity to adsorb the drugs. Furthermore, the conjugation of BN with the FA group not only improves the BN efficiency for the drug adsorption but also helps the drug-carrier complex to target the cancerous cells. Evaluation of interaction energies reveals that L-J interaction plays an essential role in the adsorption of the drug molecules on the BN. The radial distribution function (RDF) shows that the highest drug position probability is around 0.6 nm away from the BN surface. Atomic RDF analysis is in line with the interaction energy analysis and proved that π-π stacking contributes the most to this process. Hydrogen bond (HB) analysis also shows that, although limited, the columbic interaction can be helpful in the adsorption process. Moreover, the free energy (FE) surface is explored for a system containing a BN nanosheet, an FA group, and a DOX molecule through metadynamics simulations. The obtained results reveal that the lowest FE point located in coordinations d1 = 0.70 nm and d2 = 0.84 nm, and energetically reached -280.42 kJ/mol. It can be concluded from the FE calculations that while the FA is stuck on the substrate, DOX faces difficulty in the way it be adsorbed. In return, it will be hard for the molecule to be released from the BN surface through desorption processes in neutral pH because it faces an energy barrier with a height of ∼100 kJ/mol at 1.6 nm.

Asunto(s)

Antineoplásicos , Ácido Fólico , Compuestos de Boro , Doxorrubicina/farmacología

RESUMEN

Polymeric nanoparticles have emerged as efficient carriers for anticancer drug delivery because they can improve the solubility of hydrophobic drugs and also can increase the bio-distribution of drugs throughout the bloodstream. In this work, a computational study is performed on a set of new pH-sensitive polymer-drug compounds based on an intelligent polymer called poly(ß-malic acid) (PMLA). The molecular dynamics (MD) simulation is used to explore the adsorption and dynamic properties of PMLA-doxorubicin (PMLA-DOX) interaction with the graphene oxide (GOX) surface in acidic and neutral environments. The PMLA is bonded to DOX through an amide bond (PMLA-ami-DOX) and a hydrazone bond (PMLA-hz-DOX) and their adsorption behavior is compared with free DOX. Our results confirm that the polymer-drug prodrug shows unique properties. Analysis of the adsorption behavior reveals that this process is spontaneous and the most stable complex with a binding energy of -1210.262 kJ mol-1 is the GOX/PMLA-hz-DOX complex at normal pH. On the other hand, this system has a great sensitivity to pH so that in an acidic environment, its interaction with GOX became weaker while such behavior is not observed for the PMLA-ami-DOX complex. The results obtained from this study provide accurate information about the interaction of the polymer-drug compounds and nanocarriers at the atomic level, which can be useful in the design of smart drug delivery systems.