In vitro and in vivo intracellular distribution and anti-glioblastoma effects of docetaxel-loaded nanoparticles functioned with IL-13 peptide.

An active targeting delivery system helps increase intracellular drug delivery, which is promising for the treatment of glioblastoma. Interleukin 13 (IL-13) peptide which was derived from IL-13 protein could specially bind with IL-13Rα2, a receptor highly expressed on glioblastoma cells but not on normal brain cells, suggesting IL-13 peptide is an optional ligand for glioblastoma targeted therapy. In this contribution, IL-13 peptide was functionalized to nanoparticles (ILNP) to form a glioblastoma targeted drug delivery system where docetaxel was used as a model drug. The cellular uptake and intracellular delivery of ILNP indicated that IL-13 peptide facilitated cellular uptake of nanoparticles and Golgi apparatus was involved in the sorting and trafficking of ILNP rather than NP in U87 cells. Transmission electron microscopy observation revealed that ILNP mainly distributed into endosomes, cytoplasm and Golgi apparatus. In vitro apoptosis assay indicated docetaxel-loaded ILNP could induce polymerization of microtubules and produce the highest early and late apoptosis of U87 cells. Growth inhibition results of tumor spheroids demonstrated ILNP displayed the best growth inhibition of tumor spheroids. In vivo imaging suggested that ILNP accumulated significantly more in the glioma site than NP while more NP was distributed in liver, lung and spleen than ILNP. Transmission electron microscopy further demonstrated ILNP could distribute into different organelles of cells in glioma site. Thus, docetaxel loaded ILNP could induce the most apoptosis of glioma cells which was demonstrated by TUNEL. In conclusion, we presented a glioblastoma-targeting drug delivery system ILNP, which could increase the intracellular delivery of nanoparticles as well as precisely target to glioblastoma cells, and significantly increase the anti-proliferation and anti-spheroid growth effect.