Date Published: March 18, 2018
Publisher: Tabriz University of Medical Sciences
Author(s): Zahra Khatti, Seyed Majid Hashemianzadeh, Seyed Ali Shafiei.
Purpose: Drug delivery has a critical role in the treatment of cancer, in particular, carbon nanotubes for their potential use in various biomedical devices and therapies. From many other materials which could be more biocompatible and biodegradable and which could form single-walled nanotubes, silicon carbide was selected.
Carbon nanotubes (CNTs), due to their unique atomic configuration, mechanical, optical and electronic properties, have been envisioned in designing biomedical devices and therapies on novel delivery platforms.1-5 The physicochemical versatility of carbon nanotubes is related to their high surface-area-to-volume ratios and facile functionalization along the nanotube axis and a great inner content that can be filled with the desired drug molecules.6-8 Additionally, the ability of single-walled carbon nanotubes (SWCNT) to incorporate inside cells has been proven, independent of cell type and functional groups linked to the nanotubes.9,10 In vivo assays have demonstrated that SWCNTs as carriers have no obvious toxicity,11 and in animal models have demonstrated the efficacy of drug-loaded CNTs through targeting tumors.6,12 Whereas water is the main component in biological systems and CNTs are hydrophobic, heterogeneous CNTs could be considered including silicon carbide nanotube (SiCNT) in aqueous media.13 In previous studies, several advantages have been shown for SiCNTs compared to CNTs. First, there is the relative stability increase from the CNTs to SiCNTs when the ratio of Si over C is 50:50, due to alternative sp2 and sp3 hybridization bond structures that are more stable than a smooth-walled tube.14 Additionally, the external surface of SiCNTs has higher reactivity than that of CNTs to facilitate aimed side wall functionalization.15,16 Furthermore, the experimental results prove the biocompatibility of silicon nanotubes and hence an alternative option for applications in nanomedicine.17,18 Platinum-based anticancer drugs are used to treat many types of solid tumors via binding to DNA and inducing cellular apoptosis, despite their adverse side effects,19,20 so that many of these side effects for healthy cells can be greatly reduced by nanoscale drug delivery. A fast and reliable tool to evaluate theoretically such systems is molecular modeling, which could interpret the details of the interaction between the drug and both the DNA and the nanostructures.21 On the other hand, our previous study allowed the assessment of a drug delivery system caused by another nanotube apart from CNTs, as carrier on theoretical level for the first time.22 Therefore, in the present study, molecular dynamics (MD) simulation was employed to investigate another so-named nanotube SiCNT as delivery system compared to CNT. Carboplatin (diammineplatinum(II) cyclobutane-1,1-dicarboxylate) was selected as a drug model because it encompasses fewer adverse effects and has greater water solubility than other platinum agents.23-25 Our simulations have been performed to assess the encapsulation behavior and localization of the anticancer drug carboplatin inside pristine CNT and SiCNT. For this purpose, the placement of the drug inside nanotubes and the free energy calculations were implemented to determine the preference between the two predicted drug delivery systems.
The results from MD simulations of the two systems revealed that throughout the simulation time, both encapsulated carboplatin molecules resided inside the CNT and SiCNT cavity. Time-averaged radial distribution functions (RDF) were calculated to assess the localization of carboplatin inside the nanotubes (Figure 1), also RMSD plots were illustrated the drug movement inside the carbon and silicon carbide nanotubes (Figure 2). Moreover, MM/PBSA analysis of the trajectories was performed to estimate the binding free energy of the drug_CNT and the drug_SiCNT. Binding and absolute free energies of molecules are evaluated using this attractive method:
Molecular dynamic simulations to investigate the encapsulation behavior of the drug carboplatin inside the silicon carbide nanotube were applied as a comparison with the carbon nanotube as an anticancer drug delivery system based on single-walled nanotubes. The RDF plots show the localization of carboplatin inside the nanotubes, indicating that the drug moves throughout the tubes and has a greater probability of finding the carboplatin along the CNT and SiCNT in the first quarter of the tubes. Additionally, the binding free energy profiles in the encapsulation of drug inside both systems were investigated. The results confirmed that the appropriate drug delivery system for platinum drug is the use of SiCNTs to CNTs. Since the free energy of binding in the silicon carbide nanotube is about three times that of the carbon nanotube, the length of time remaining for the drug in this system will be greater, and the probability of releasing the drug will be less than with carbon nanotube, before reaching the target cells.
The authors give special thanks to S. Skies for editing this manuscript.
The authors declare no conflict of interests.