科研之友
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摘要
A combination of gene therapy and chemotherapy has recently received interest as a targeted therapy for glioma. A mesoporous silica nanoparticle (MSN)-based vehicle coated with IL13R alpha 2-targeted peptide (IP) using polyethylene glycol (PEG), MSN-PEG-IP (MPI), was constructed and confirmed as a potential glioma-targeted drug delivery system in vitro. In this work, tissue microarray (TMA) results revealed that IL13R alpha 2 was over-expressed in human glioma tissues and that high expression of IL13R alpha 2 in patients was associated with poor survival. Doxorubicin (DOX)-loaded MPI (MPI/D) crossed the blood-brain barrier, specifically targeting glioma cells and significantly enhancing the cellular uptake of DOX in glioma cells compared with MSN/DOX (M/D) and MSN-PEG/DOX (MP/D), whereas the normal brain was not affected. Magnetic Resonance Imaging (MRI) examinations showed that the tumour size of glioma-bearing rats in the MPI/D-treated group was much smaller than those in the M/D and MP/D treated groups. Immunofluorescence results demonstrated that MPI/D treatment induced more apoptosis and much less proliferation than the other two treatments. However, the therapeutic effect was weak when IL13R alpha 2 was knocked down. Furthermore, U87 cells treated with IL-13 and MPI together could increase both STAT6 and P63 expression, which attenuated glioma cell proliferation, invasion and migration compared with cells treated with IL-13 alone. The results of the subcutaneous tumour model also revealed that IL13R alpha 2 knockdown could hinder cell proliferation and induce more apoptosis. The promising results suggested that MPI can not only deliver DOX to glioma in a targeted manner but also occupy IL13R alpha 2, which can promote IL-13 binding to IL13R alpha 1 and activation of the JAK-STAT pathway to induce an anti-glioma effect.
