Mixed surfactant modified graphene oxide nanocarriers for DOX delivery to cisplatin-resistant human ovarian carcinoma cells

Abstract

The non-covalent functionalization of graphene oxide (GO) with hydroxyethyl cellulose (HEC, nonionic surfactant) and polyanionic cellulose (PAC, anionic surfactant) was developed for anti-cancer drug delivery applications based on a nonideal mixed micelle theory of surfactants. In order to maintain the stability of GO in aqueous electrolytes, the optimal component of the mixed surfactant modified nanocarriers (GO–PAC/HEC) was determined via a multi-factors orthogonal method. Benefiting from the enormous specific surface area of GO and π–π stacking interactions, doxorubicin hydrochloride (DOX), a model anticancer drug, was loaded onto the GO–PAC/HEC surface with high drug loading. The most appropriate loading content of DOX on GO–PAC/HEC was obtained by zeta potential evaluation and a stability time test. The in vitro DOX release profiles from DOX-loaded nanocarriers (GO–PAC/HEC–DOX) exhibited a significant pH-responsive feature and satisfactory performance of drug controlled release. Moreover, in vitro investigation showed that DOX-loaded nanoparticles entered into and treated cancer cells effectively and enhanced the accumulation of DOX in SKOV3/DDP cells (cisplatin-resistant human ovarian carcinoma cell line) exhibiting higher cytotoxicity than free DOX, suggesting that DOX-loaded nanoparticles may overcome DOX resistance of SKOV3/DDP cells to some extent. Based on the results obtained in this study, GO–PAC/HEC shows considerable potential as a drug delivery vehicle.