Tumor cell targeted delivery by specific peptide-modified mesoporous silicananoparticles

Abstract

Receptor-mediated delivery of hydrophobic antitumor drugs is of great interest in chemotherapy of tumors such as glioma. Specific expression of interleukin-13 (IL-13) receptor has been characterized in glioma. In this work, a specific peptide corresponding to the residues within IL-13 protein, designated as IP, was exploited, for the first time, as a glioma-targeting ligand. IP was conjugated to mesoporous silica nanoparticles (MSN) via bifunctional polyethyleneglycol (PEG), constructing the vector MSN–PEG–IP. The successful synthesis of MSN–PEG–IP was demonstrated via Fourier transform infrared spectroscopy. The transmission electron microscopy result showed that the size of MSN–PEG–IP was about 160 nm with an average pore diameter of around 2.6 nm. The cellular uptake of doxorubicin (DOX)-loading IP-modified system (MSN–PEG–IP/DOX) was concentration-dependent in glioma U251 cells. IP modification could significantly enhance the cellular uptake of the drug delivery system in U251 cells but not in normal astrocyte 1800 cells, compared to unmodified counterparts. This effect was further verified by cytotoxicity analysis. Furthermore, the intracellular trafficking result indicated that the loaded DOX was mostly accumulated in nuclei, even at very short incubation time (5 min). All the results suggested that IP could be applied as a special glioma-targeting ligand, and MSN–PEG–IP is a potential vector for delivering hydrophobic chemotherapeutic drugs to IL-13 receptor-overexpressed tumors.