Graphene Oxide Hosting a pH-Sensitive Prodrug: An In Silico Investigation of Graphene Oxide-Based Nanovehicle toward Cancer Therapy.

Prodrug and drug delivery systems are two effective strategies for improving the selectivity of chemotherapeutics. Herein, via molecular dynamics (MD) simulation and free energy calculation, the effectiveness of the graphene oxide (GO) decorated with the pH-sensitive prodrug (PD) molecules in cancer therapy is investigated. PEI-CA-DOX (prodrug) was loaded onto the GO surface, in which the hydrogen bonding and pi-pi stacking interactions play the main role in the stability of the GO-PD complex. Due to the strong interaction of GO and PD (about -800 kJ/mol), the GO-PD complex remains stable during the membrane penetration process. The obtained results confirm that GO is a suitable surface for hosting the prodrug and passing it through the membrane. Furthermore, the investigation of the release process shows that the PD can be released under acidic conditions. This phenomenon is due to the reduction of the contribution of electrostatic energy in the GO and PD interaction and the entry of water into the drug delivery system. Moreover, it is found that an external electrical field does not have much effect on drug release. Our results provide a deep understanding of the prodrug delivery systems, which helps the combination of nanocarriers and modified chemotherapy drugs in the future.