Nanoparticles functionalized with Pep-1 as potential glioma targeting delivery system via interleukin 13 receptor α2-mediated endocytosis.

The treatment for glioma is one of the most challenging problems and therapeutic effect of glioma is often limited due to poor penetration into the tumor tissue. Interleukin 13 receptor α2 (IL-13Rα2) is over-expressed on tumor including established glioma cell lines and primary glioblastoma cell cultures. However, it will not cause activation of its signaling pathways. So it could be served as a promising targeted moiety for anti-glioma drug delivery. Pep-1, one specific ligand of IL-13Rα2, was identified to exhibit excellent capacity of crossing the blood tumor barrier (BTB) and homing to giloma. In this study, based on the IL-13Rα2-mediated endocytosis, Pep-1 was exploited as a potential ligand for effective glioma-targeting delivery. Pep-1 was functionalized to the surface of PEG-PLGA nanoparticles (Pep-NP) to evaluate its glioma homing, by taking advantage of the excessive expression of the IL-13Rα2 on the surface of glioma cells. Compared with non-targeting nanoparticles, Pep-NP exhibited a significantly enhanced cellular association in rat C6 glioma cells and improved penetration in 3D avascular C6 glioma spheroids. Following intravenous administration, Pep-NP could facilitate the distribution of the coumarin-6 in vivo glioma region, 2.21 times higher than that of NP for quantitative analysis. In conclusion, the Pep-NP could precisely target to the brain glioma, which was a potential targeting drug delivery system for glioma treatment.