Chemically Modified Carbon Nanohorns as Nanovectors of the Cisplatin Drug: A Molecular Dynamics Study

Abstract

Carbon nanohorns (CNH) have been considered potential anticancer drug carriers, such as the cisplatin drug (cddp), due to their low toxicity, high purity, drug-loading capacity, and biodegradation routes. However, when it comes to nanomedicine applications, chemical functionalization is an essential step in order to overcome undesirable properties of these nanomaterials, such as the high hydrophobicity, low reactivity, and low dispersibility in polar solvents. In this context, the present study involved the modeling of new CNH topologies based on chemical oxidation and reduction mechanisms and the investigation of the influence of these modified structures on the dynamics and stability of inclusion complexes with cddp. The results indicated that these functionalization strategies lead to the opening of nanowindows on the CNH surfaces, which would constitute the main route for drug release, as reported by experimentalists. Also, our results showed that the insertion of polar functional groups on the oxidized CNH (CNHox-N) contributed to an improvement of the cddp@CNHox-N biocompatibility due to the greater number of hydrogen bonds formed with the solvent. Despite the favorable formation of all complexes, the binding free energies pointed out that the oxidation process made the cddp@CNHox-N complexes slightly less stable than the ones with pristine and reduced CNH. Besides, the results suggest the possibility to tune the complex stability by controlling the oxidation degree, which could be explored by the experimentalists in order to design controlled drug delivery systems based on CNH nanocarriers.

Application of a quantum genetic algorithm and QTAIM analysis in the study of structural and electronic properties of neutral bimetallic clusters NaxLiy (4 ≤ x + y ≤ 10)

“…A nano-sized cluster of atoms or molecules has a particular set of properties that depends on its composition and size-a distinguishing feature when compared to the condensed matter [1,2]. The understanding of these properties has allowed the design of a wide range of nanomaterials, which are applied in medicine [1,[3][4][5][6][7][8][9][10][11][12][13][14], catalysis [11,13], semiconductors materials [15][16][17][18][19], fuel cells [16,20], etc. A prominent class of nanomaterials is the nanoalloy which may exhibit distinct properties from the pure metal clusters and it has application in the electronics and engineering fields [2,21].…”

1H and 195Pt NMR prediction for inclusion compounds formed by cisplatin and oxidized carbon nanostructures

“…5a-d, it was possible to conclude that, on average, the plane dened by the square planar geometry of the cDDP molecule remained parallel to the main axis of the carbon nanostructure, as well reported in our recent MD simulations results. 27,72 In addition, NH 3 groups of cisplatin also remained close to the oxidized region of the CNTox. The same spatial conguration was also observed in our inclusion complexes involving pristine, 27 oxidized, and reduced CNH topologies.…”

“…S3, ESI †), as also concluded in our recent works with similar systems. 27,72 The RMSD value of 0.32 AE 0.05Å suggests a structural stability of this complex.…”

“…In order to analyze the explicit solvent effect on the calculation of NMR chemical shis, we performed a MD simulation of the cDDP@CNTox complex in explicit solvent (water molecules). Specically, the cDDP@CNTox model was selected as a prototype for this analysis which involved the same parameterization procedure and simulation protocol recently employed in our works 27,72 and, moreover, in this work it represents the most energetically favorable model.…”

“…4a, the rst peak at 2.55Å indicated the presence of water molecules inside the cavity of nanotube forming an inner solvation shell as previously reported by our group for the carbon nanocones models. 27,72 By computing the integral over this rst peak, we found a coordination number equals to 2 from the analysis of the red dot line. This means that, on average, there are 2 water molecules distributed around the CM of CNTox.…”