Protein–protein interactions between SWCNT/chitosan/EGF and EGF receptor: a model of drug delivery system

Abstract

Epidermal growth factor (EGF) was used as the targeting ligand to enhance the specificity of a cancer drug delivery system (DDS) via its specific interaction with the EGF receptor (EGFR) that is overexpressed on the surface of some cancer cells. To investigate the intermolecular interaction and binding affinity between the EGF-conjugated DDS and the EGFR, 50 ns molecular dynamics simulations were performed on the complex of tethered EGFR and EGF linked to single-wall carbon nanotube (SWCNT) through a biopolymer chitosan wrapping the tube outer surface (EGFR·EGF-CS-SWCNT-Drug complex), and compared to the EGFR·EGF complex and free EGFR. The binding pattern of the EGF-CS-SWCNT-Drug complex to the EGFR was broadly comparable to that for EGF, but the binding affinity of the EGF-CS-SWCNT-Drug complex was predicted to be somewhat better than that for EGF alone. Additionally, the chitosan chain could prevent undesired interactions of SWCNT at the binding pocket region. Therefore, EGF connected to SWCNT via a chitosan linker is a seemingly good formulation for developing a smart DDS served as part of an alternative cancer therapy.

Keywords:

• drug delivery system
• epidermal growth factor receptor-targeted agent
• chitosan-modified carbon nanotube
• molecular dynamics

Acknowledgments

The computing facilities were provided by the Computational Chemistry Unit Cell, Faculty of Science, Chulalongkorn University and High Performance Computing Services of National Electronics and Computer Technology Center (NECTEC), Thailand.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Thailand Research Fund [grant number IRG5780008]; National Research University Project, Office of Higher Education Commission [grant number WCU-031-AM-57].