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

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

Acknowledgment

This work was supported by the National Key Basic Research Program (2010CB732404) and the National Nature Science Foundation of China (30740062, 30872970).

Disclosure

The authors report no conflicts of interest in this work.