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 strategiesfor improving the selectivity of chemotherapeutics. Herein, via moleculardynamics (MD) simulation and free energy calculation, the effectivenessof 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 bondingand pi-pi stacking interactions play the main role in the stabilityof the GO-PD complex. Due to the strong interaction of GO andPD (about -800 kJ/mol), the GO-PD complex remains stableduring the membrane penetration process. The obtained results confirmthat GO is a suitable surface for hosting the prodrug and passingit through the membrane. Furthermore, the investigation of the releaseprocess shows that the PD can be released under acidic conditions.This phenomenon is due to the reduction of the contribution of electrostaticenergy in the GO and PD interaction and the entry of water into thedrug delivery system. Moreover, it is found that an external electricalfield does not have much effect on drug release. Our results providea deep understanding of the prodrug delivery systems, which helpsthe combination of nanocarriers and modified chemotherapy drugs inthe future.