A new insight into the transfer and delivery of anti-SARS-CoV-2 drug Carmofur with the assistance of graphene oxide quantum dot as a highly efficient nanovector toward COVID-19 by molecular dynamics simulation.

Currently, a preventive and curative treatment for COVID-19 is an urgent global issue. According to the fact that nanomaterial-based drug delivery systems as risk-free approaches for successful therapeutic strategies may led to immunization against COVID-19 pandemic, the delivery of Carmofur as a potential drug for the SARS-CoV-2 treatment via graphene oxide quantum dots (GOQDs) was investigated in silico using molecular dynamics (MD) simulation. MD simulation showed that π-π stacking together with hydrogen bonding played vital roles in the stability of the Carmofur-GOQD complex. Spontaneous attraction of GOQDs loaded with Carmofur toward the binding pocket of the main protease (Mpro) resulted in the penetration of Carmofur into the active catalytic region. It was found that the presence of GOQD as an effective carrier in the loading and delivery of Carmofur inhibitor affected the structural conformation of Mpro. Higher RMSF values of the key residues of the active site indicated their greater displacement to adopt Carmofur. These results suggested that the binding pocket of Mpro is not stable during the interaction with the Carmofur-GOQD complex. This study provided insights into the potential application of graphene oxide quantum dots as an effective Carmofur drug delivery system for the treatment of COVID-19.

The performance of the single-walled carbon nanotube covalently modified with polyethylene glycol to delivery of Gemcitabine anticancer drug in the aqueous environment.

A computational investigation of Gemcitabine drug adsorption on the single-walled carbon nanotube covalently modified with polyethylene glycol in a series of the configurations is studied using density functional theory calculations. It is observed that O…H hydrogen bonds are the dominating intermolecular interactions during the complex formation between anti-cancer drug and the nanotube. The studied hydrogen-bonded complexes are treated theoretically to elucidate the nature of the intermolecular hydrogen bonds, geometrical structures, the binding energy and electron density topological analysis. The existence of the bond critical points between hydrogen and the electronegative atoms and their concomitant bond paths which connect the bond critical points to the two interacting atoms confirm by Quantum Theory of Atoms in Molecules method. In addition, considering the charge transfer for all of the adsorbed configurations reveals the capability of the drug molecule to accept precisely the electron from the functionalized carbon nanotube during the drug adsorption on external surface of the carbon nanotube. Also, the effect of weight percent of polyethylene glycol on the drug adsorption strength is investigated by molecular dynamics simulations. Communicated by Ramaswamy H. Sarma.

Theoretical investigation insights into the temperature triggered tegafur anticancer drug release from the surface of graphene oxide nanosheet.

In order to quantitatively account of tegafur drug interaction with graphene oxide nanosheet, various geometrical structures are examined to study the detailed effects of drug adsorption on the structural properties, interaction energy and charge transfer of the studied complexes at the microscopic level using the density functional theory study. The bond paths at the quantum theory of atoms in molecules' bond critical points show that the considered complexes are stabilized by the O…H hydrogen bond intermolecular interactions. In addition, the molecular dynamics simulations are applied to simulate drug release in response to the temperature change in the physiological pH. The increasing the temperature of the simulation system from 310 to 315 K has the effect of decreasing the strength of intermolecular attraction and subsequently, liberation of the adsorbed drugs from the surface of the nanosheet is observed.Communicated by Ramaswamy H. Sarma.

Predicting doxorubicin drug delivery by single-walled carbon nanotube through cell membrane in the absence and presence of nicotine molecules: a molecular dynamics simulation study.

In order to study the interaction of the anticancer agent Doxorubicin with the single-walled carbon nanotubes with different diameters as drug delivery systems, the molecular dynamics (MD) simulations have been used. Also, for design and development of intracellular Doxorubicin drug delivery systems, a series of steered MD simulations are applied to explore the possibility of encapsulated Doxorubicin-carbon nanotube penetration through a lipid bilayer in presence and absence of Nicotine molecules at different pulling rates. Our simulation results showed that in spite of the adsorption of drug molecules on the outer sidewall of the nanotubes, the spontaneous localization of one Doxorubicin molecule into the cavity of the nanovectors with larger diameters is observed. It is found that the presence of Nicotine molecules in extracellular medium increases the required force for pulling nanotube-encapsulated drug as well as the required time for penetration process, especially at higher velocity. Also, the entering process of the Nicotine molecules into the carbon nanotube causes that the encapsulated drug molecule is fully released in the hydrophobic phase of the lipid bilayer.Communicated by Ramaswamy H. Sarma.

Assessment of dynamical properties of mercaptopurine on the peptide-based metal-organic framework in response to experience of external electrical fields: a molecular dynamics simulation.

In this work, the effect of the external electric field (EF) on the drug delivery performance of peptide-based metal-organic framework (MPF) for 6-mercaptopurine (6-MP) drug is investigated by means of the molecular dynamics (MD) simulations. It is found that the strength interaction of drug molecule with MPF is decreased under the influence of the electric field. In other words, the adsorbed drug molecules have more tendencies for the interaction with the porous nanostructure in the absence of EF. According to the radial distribution function (RDF) patterns, the probability of finding drug molecules in terms of the intermolecular distance with respect to the MPF surface is lowest during the high field strength. As the EF strength increases, the spread of drug molecules around MPF results in high dynamics movement and further more diffusion coefficient of drug molecule in the simulation system. This result emphasizes the weak intermolecular interaction of drug molecules with MPF with the application of EF. Assessment of dynamical properties of 6-mercaptopurine in the presence of EF with various strengths reveals that the applied electric field can act as a trigger on liberation behavior of drug from the porous nanostructure.

Comparative prediction of binding affinity of Hydroxyurea anti-cancer to boron nitride and carbon nanotubes as smart targeted drug delivery vehicles.

In this study, the adsorption of Hydroxyurea (HU) onto the inner and outer surfaces of boron nitride and carbon nanotubes (CNTs) was investigated using the density functional theory calculations and molecular dynamics (MDs) simulations in aqueous solution. The values of the adsorption energy show that HU molecule is preferentially adsorbed inside of boron nitride and CNTs with the molecular axis parallel to the tubes axis, which means that the cavity of nanotubes is favorable for encapsulation of this drug. Also, it was found that the HU/boron nitride nanotube (BNNT) system is more stable than the HU/CNT system. The stability of the complexes of HU/ BNNT attributed to the formation of the intermolecular hydrogen bonds between the H atoms of HU molecule and the N atoms of BNNT, which is confirmed by Bader's quantum theory of atoms in molecules. The natural bond orbital analysis shows the charge transfers occur from HU molecule to nanotubes in all complexes. Moreover, the adsorption of HU molecule on the surfaces of the nanotubes was investigated by explicit water models. Also, the adsorption behavior of HU on the functionalized boron nitride and CNTs is investigated to design and develop new nanocarriers for biomedical applications. Furthermore, MDs simulations are examined in the presence of one and two drug molecules. The obtained results illustrate that the lowest value of Lennard-Jones (L-J) energy between drug and nanotubes exist in the simulation system with two drug molecules.

The computational study of the γ-Fe2O3 nanoparticle as Carmustine drug delivery system: DFT approach.

In the present study, it is attempted to scrutinize the properties of the maghemite nanoparticle as a Carmustine drug delivery system by means of the density functional theory calculations regarding their geometries, adsorption energies, vibrational frequencies, and topological features of the electron density. Based on the density functional theory results, it is found that the interaction between Carmustine drug molecule and maghemite nanoparticle is weak; so that, the adsorption of the Carmustine drug is typically physisorption. It is also found that the intermolecular hydrogen bonds between the drug and the nanoparticle play the significant role in the stability of the physisorption configurations. The nature of the intermolecular interactions has been explored by calculation of the electron densities and their Laplacian at the bond critical points using Atoms-in-Molecule theory. Moreover, natural bond orbital analysis indicates that the Carmustine molecule can be adsorbed on the nanoparticle surface with a charge transfer from the Carmustine drug to the nanoparticle.

Screening of the structural, topological, and electronic properties of the functionalized Graphene nanosheets as potential Tegafur anticancer drug carriers using DFT method.

In the present work, we apply comprehensive theoretical calculations in order to study Tegafur drug adsorption on the nanostructured functionalized Graphene with hydroxyl, epoxide, carbonyl, and carboxyl groups in the water environment. The physical nature of Tegafur adsorption offers advantages in terms of easy desorption of anticancer molecule with no structural or electronic change of the adsorbed drug. By functionalization of Graphene nanosheet with a carbonyl group, a considerable increase on the binding energy between Tegafur drug and the nanosheet is noted. Diminish in energy gap with the adsorption of Tegafur drug on the functionalized nanosheets shows that the reactivity of functionalized complexes increases upon loading of the drug molecule. Besides, the adsorption process yields an increase of the polarity which causes the possibility of the solubility and dispersion of the considered complexes enhances. This result is indicative the suitability of the nanomaterials toward Tegafur drug delivery within the biological environments. The high solvation energy of Tegafur anticancer drug adsorbed functionalized Graphene models enforced their applicability as nanocarriers in the living system. These results are extremely relevant that the chemical modification of Graphene nanosheet using covalent functionalization scheme is an effectual approach for loading and delivery of Tegafur drug molecule within biological systems.