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

Haijun Zhang¹, Cailian Wang¹, Baoan Chen^2,3, Xuemei Wang^3,4
1Department 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 China

Abstract: 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