Highly water-dispersible TiO2nanoparticles for doxorubicin delivery: effect of loading mode on therapeutic efficacy

Abstract

Highly water-dispersible titanium dioxide (TiO₂) nanoparticles with abundant carboxyl groups were synthesized through a ligand exchange method. Chemotherapeutic doxorubicin (DOX) was then loaded on the TiO₂ nanoparticles by non-covalent complexation (TiO₂/DOX) or covalent conjugation (TiO₂-DOX). The cytotoxicity, cellular uptake, and intracellular location of the two formulations were evaluated in C6 glioma cells. Our results showed that TiO₂/DOX exhibited a greater cytotoxicity toward C6 cells than free DOX, while TiO₂-DOX showed decreased cytotoxicity. A higher cellular uptake of TiO₂-DOX was correlated with greater cytotoxicity of TiO₂/DOX. In addition, confocal laser scanning microscopy demonstrated that most of the DOX was located inside the nuclei in TiO₂/DOX. In contrast, TiO₂-DOX was predominantly distributed in the cytoplasm. Thus, our work demonstrates that the therapeutic efficacy of TiO₂-loaded DOX is strongly dependent on its loading mode and this provides important information for the future applications of TiO₂ as a drug carrier.