Non-porous phosphonated ionic silica nanospheres as nanocarriers for efficient intracellular delivery of doxorubicin

Abstract

A novel nanoscale drug delivery system based on monodispersed non-porous ionic silica nanospheres (NISNs) decorated with phosphonated active sides homogeneously distributed all over their surface, was developed. Doxorubicin (DOX), a well-known antitumor drug, was successfully loaded on the surface of the silica nanoparticles via electrostatic interactions. The final drug vehicle possesses excellent solubility, while enhancing significantly the efficacy of the drug. The administration of DOX-loaded NISNs against two aggressive DOX-resistant human prostate adenocarcinoma cell lines DU145 and PC3 leads to increased medicinal efficacy with extremely low DOX concentrations (0.1 μM) that could significantly reduce DOX side effects. In addition, NISNs was found to be non-toxic. The efficient cellular uptake of NISNs_DOX was confirmed by flow cytometry analysis and visualized by confocal microscopy. The translocation of DOX inside cells drastically changed, when DOX was bound to NISNs nanoparticles. Specifically, DOX loaded to NISNs nanoparticles is preferentially localized in the cytosol and significant efficacy was observed due to slow controlled release of DOX to the nucleus. The results reported in this work strongly support the potential utilization of NISNs derivatives as non-toxic nanocarriers for high loading efficiency and intracellular delivery of therapeutic drugs.