Stabilization of Doxorubicin Drug on Graphene Oxide Nanosystem and Computer simulation Study (In-Silico) on Topoisomerase II Enzyme

Subject Areas : journal of New Materials

Sedigheh Pargaleh boroujeni ¹ , Nooreddin Goodarzian ² , Neda Hasanzadeh ³ , Mohammad Kazem Mohammadi ⁴

1 - Department of Chemistry, Ahvaz Science and Research branch, Islamic Azad University, Ahvaz, Iran
2 - Department of Chemistry, Shiraz Branch, Islamic Azad University, Shiraz, Iran
3 - Department of Chemistry, Ahvaz Science and Research branch, Islamic Azad University, Ahvaz, Iran
4 - Department of Chemistry, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran

Received: 2024-07-02 Accepted : 2024-09-16 Published : 2024-10-14

Keywords: Doxorubicin, Graphene Oxide, Topoisomerase II Enzyme, Release, Nano System,

Abstract :

Introduction Doxorubicin is a well-known anticancer drug that has been the focus of numerous studies aimed at enhancing its efficacy and enabling targeted drug delivery, thereby transforming it into an effective nanomedicine. The objectives of this study included the stabilization of doxorubicin on a graphene oxide nanosystem and analyzing various properties related to this stabilization, as well as conducting in-silico studies of this drug on topoisomerase II enzyme. To investigate the effects of doxorubicin on the graphene oxide substrate, graphene oxide was first synthesized from graphite using the Hummers method. Following this, doxorubicin loading was achieved by sonication, thus stabilizing the drug on the substrate. Doxorubicin hydrochloride was also used as a standard.

Methods: To evaluate the properties of the stabilized drug, FT-IR, SEM, and X-ray diffraction (XRD) analyses were employed. For studying the molecular interactions of the obtained compound with topoisomerase II enzyme, molecular docking was utilized. Among 50 clusters considered for the compound, the 40th cluster exhibited the best energy state of -2.9 kcal/mol. Furthermore, the intramolecular energy, electrostatic energy, overall internal energy, and torsional free energy at 298.15 Kelvin were reported as -18.6 kcal/mol, -0.91 kcal/mol, -14.4 kcal/mol, and -28.3 kcal/mol, respectively.

 

Findings: The best interactions were attributed to van der Waals, hydrogen, hydrogen-carbon, alkyl, and π-alkyl bonds. In this context, a total of 13 amino acids remained in contact with the drug. In the infrared spectrum analysis, an increased intensity of the stretching vibrations of the hydrogen atoms in the first-type aliphatic amine group was observed in the FTIR peaks, providing evidence for the drug's stabilization on the graphene substrate due to greater freedom of action of the relevant hydrogen atoms and their activation resulting from interaction with the graphene oxide substrate. Additionally, a shift in the stretching vibration position of the carbonyl group from 1608 cm⁻¹ towards lower wavenumbers was observed due to the attack of the lone pair electrons of the oxygen atoms on the carbonyl backbone of the doxorubicin molecules. According to SEM and FESEM spectra, the stabilized drug on both GO and rGO samples exhibited a roughly layered and heterogeneous structure. After the reduction process, the rGO structure appeared as more uniform and smoother sheets, which was attributed to the reduction of oxygen groups in rGO, leading to increased uniformity and reduced surface roughness. XRD data revealed a strong peak in GO corresponding to the interlayer spacing (d-spacing), indicating a layered structure and the presence of oxygen groups on the GO surface. Conversely, in the XRD spectrum of rGO, a peak around 26-27 degrees was observed, reflecting the reduction of the interlayer spacing (d-spacing) due to the removal of oxygen groups and increased structural uniformity.

The diffraction pattern of rGO displayed a simpler and more uniform spectrum, signifying improved crystalline structure and reduced systemic defects. Based on the favorable instrumental results and in-silico studies on topoisomerase II, along with the high importance of biocompatibility of drug carriers, the superiority of the stabilized doxorubicin drug on the graphene oxide nanosystem compared to the initial drug is evident, and the recent compounds can be considered suitable candidates for further improving cancer patients' treatment and controlling their diseases.

 

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