Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles

Abstract

Yan Chen1,*, Ying Wan1,*, Yi Wang1, Haijun Zhang2, Zhijun Jiao11Key Laboratory of Medical Immunology and Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang; 2Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China *These authors have contributed equally to this workBackground: Doxorubicin has a broad spectrum of anticancer activity, but its clinical application is limited due to serious side effects. The aim of this study was to explore a novel drug delivery system based on titanium dioxide (TiO2) nanoparticles for its potential role in enhancing the anticancer efficacy of doxorubicin while reducing its side effects.Methods and results: Doxorubicin was loaded into TiO2 nanoparticles by forming complexes with the transition metal, titanium, to construct doxorubicin-titanium dioxide (DOX-TiO2) nanocomposites as a drug delivery system. The anticancer activity of the DOX-TiO2 nanocomposites was demonstrated by MTT assay, and the possible signaling pathway was explored by Western blot. In human SMMC-7721 hepatocarcinoma cells, our observations demonstrated that this drug delivery system markedly increased the efficiency of drug per dosage and decreased the IC50, resulting in anticancer efficacy enhancement and side effect attenuation.Conclusion: Such a doxorubicin delivery strategy is promising in cancer therapy. Apoptosis may contribute to the mechanism, due to protein expression of Bcl-2 being downregulated and that of Bax and caspase 3 being upregulated.Keywords: doxorubicin, titanium dioxide nanoparticles, drug delivery system, apoptosis