Hollow chitosan-silica nanospheres for doxorubicin delivery to cancer cells with enhanced antitumor effect in vivo

Here we report the synthesis of hybrid hollow chitosan-silica nanospheres (CS-Silica NPs) with chitosan-polyacrylic acid (CS-PAA) nanoparticles as the template and doxorubicin (DOX) delivery based on CS-Silica NPs. The morphology and the microstructure of CS-Silica NPs were characterized by field emission scanning electron microscopy (FESEM) and X-ray photoelectron spectroscopy (XPS). The confocal laser scanning microscopy (CLSM) and flow cytometry experiments showed that the cellular uptake of the DOX-loaded CS-Silica NPs was time dependent. In addition, cellular internalization and intracellular distribution of DOX-loaded CS-Silica NPs indicated that the DOX was mainly distributed in the cell nucleus while the carriers were primarily located in the cytoplasm. In vivo antitumor response indicated that the DOX loaded CS-Silica hybrid hollow nanospheres exhibited superior antitumor effect over the free drug in vivo, which might be ascribable to the enhanced cellular uptake efficiency and the effective delivery of drug to the cell nucleus.