Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using cetuximab-conjugated iron-oxide nanoparticles.

摘要: Malignant gliomas remain aggressive and lethal primary brain tumors in adults. The epidermal growth factor receptor (EGFR) is frequently overexpressed the most common malignant glioma, glioblastoma (GBM), represents an important therapeutic target. GBM stem-like cells (GSCs) present are felt to be highly tumorigenic responsible for tumor recurrence. Multifunctional magnetic iron-oxide nanoparticles (IONPs) can directly imaged by resonance imaging (MRI) designed therapeutically target cancer cells. targeting effects of IONPs conjugated EGFR inhibitor, cetuximab (cetuximab-IONPs), were determined with EGFR- EGFRvIII-expressing human neurospheres GSCs. Transmission electron microscopy revealed cetuximab-IONP cell binding internalization. Fluorescence Prussian blue staining showed increased uptake cetuximab-IONPs as well GSCs comparison or free IONPs. Treatment resulted a significant antitumor effect that was greater than alone due more efficient, CD133-independent cellular uptake, signaling alterations, internalization, apoptosis induction EGFR-expressing neurospheres. A increase survival found after convection-enhanced delivery treatment 3 intracranial rodent models employing xenografts.