Daunorubicin-TiO2 nanocomposites as a “smart” pH-responsive drug delivery system

Abstract

Haijun Zhang1, Cailian Wang1, Baoan Chen2,3, Xuemei Wang3,41Department of Oncology, Zhongda Hospital, Medical School, 2Department of Hematology, Zhongda Hospital, Medical School, 3Faculty of Oncology, Medical School, 4State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People’s Republic of ChinaAbstract: Daunorubicin (DNR) has a broad spectrum of anticancer activity, but is limited in clinical application due to its serious side effects. The aim of this study was to explore a novel “smart” pH-responsive drug delivery system (DDS) based on titanium dioxide (TiO2) nanoparticles for its potential in enabling more intelligent controlled release and enhancing chemotherapeutic efficiency of DNR. DNR was loaded onto TiO2 nanoparticles by forming complexes with transition metal titanium to construct DNR-TiO2 nanocomposites as a DDS. DNR was released from the DDS much more rapidly at pH 5.0 and 6.0 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. DNR-TiO2 nanocomposites induced remarkable improvement in anticancer activity, as demonstrated by flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and nuclear 4′,6-diamidino-2-phenylindole staining. Furthermore, the possible signaling pathway was explored by western blot. For instance, in human leukemia K562 cells, it was demonstrated that DNR-TiO2 nanocomposites increase intracellular concentration of DNR and enhance its anticancer efficiency by inducing apoptosis in a caspase-dependent manner, indicating that DNR-TiO2 nanocomposites could act as an efficient DDS importing DNR into target cancer cells. These findings suggest that “smart” DNR delivery strategy is a promising approach to cancer therapy.Keywords: drug delivery system, daunorubicin, pH-responsive, TiO2 nanoparticles, cancer, apoptosis