Engineered nanoparticles as Selinexor drug delivery systems across the cell membrane and related signaling pathways in cancer cells

• Published in: Journal of molecular graphics & modelling 2024-09, Vol.131, p.108809, Article 108809
• Main Authors: Nakhaei, Alireza, Raissi, Heidar, Farzad, Farzaneh
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological membrane; Cell Membrane - chemistry; Cell Membrane - metabolism; Classical molecular dynamics simulation; Drug Carriers - chemistry; Drug delivery; Drug Delivery Systems - methods; Graphene oxide nanoflake; Graphite - chemistry; Humans; Hydrazines - chemistry; Hydrogen Bonding; Metadynamics; Molecular Dynamics Simulation; Nanoparticles - chemistry; Neoplasms - drug therapy; Selinexor; Signal Transduction - drug effects; SMD simulation; Triazoles - chemistry
• ISSN: 1093-3263; 1873-4243; 1873-4243
• DOI: 10.1016/j.jmgm.2024.108809

In the present work, molecular dynamics simulation is applied to evaluate the drug carrier efficiency of graphene oxide nanoflake (GONF) for loading of Selinexor (SXR) drug as well as the drug delivery by 2D material through the membrane in aqueous solution. In addition, to investigate the adsorption and penetration of drug-nanocarrier complex into the cell membrane, well-tempered metadynamics simulations and steered molecular dynamics (SMD) simulations were performed. Based on the obtained results, it is evident that intermolecular hydrogen bonds (HBs) and π-π interactions play a significant role in expediting the interaction between drug molecules and the graphene oxide (GO) nanosheet, ultimately resulting in the formation of a stable SXR-GO complex. The Lennard-Jones (L-J) energy value for the interaction of SXR with GONF is calculated to be approximately −98.85 kJ/mol. In the SXR-GONF complex system, the dominant interaction between SXR and GONF is attributed to the L-J term, resulting from the formation of a strong π−π interaction between the drug molecules and the substrate surface. Moreover, our simulations show by decreasing the distance of GONF with respect to cell membrane, the interaction energy of GONF-membrane significantly decrease to −1500 kJ/mol resulting in fast diffusion of SXR-GONF complex toward the bilayer surface that is favored opening the way to natural drug nanocapsule. [Display omitted] •Molecular dynamic simulation is examined the drug delivery systems.•Engineered nanoparticles as Selinexor drug delivery systems were introduced.•Ability of graphene oxide nanoflake to vectorize Selinexor drugs is introduced.•Drug delivery by two-dimensional graphene oxide across the cell membrane is introduced.•The mechanism of the SXR drug loading process onto the surface of GONF is investigated.