Anti-CD133 monoclonal antibody conjugated immunomagnetic nanosensor for molecular imaging of targeted cancer stem cells

Abstract Magnetic nanosensors are considered as highly attractive platforms for effective treatments in cancer diagnosis and therapy. Herein a smart immunomagnetic nanosensor is novelly developed for molecular imaging of targeted glioblastoma cancer stem cells (CSCs), based on specific interaction between cell-membrane marker antigen CD133 of glioblastoma CSCs and its raised anti-CD133 monoclonal antibody (mAb). Superparamagnetic iron oxide (SPIO) γ-Fe 2 O 3 nanoparticles (NPs) were fabricated as nanosensor cores with approximately 10–15 nm in size, and coated with carboxymethyl chitosan (CMCS) via sodium tripolyphosphate (TPP) crosslinking, and then chemically modified with polyethylenimine (PEI). Anti-CD133 mAb, specific affinity with the cancer stem biomarker CD133 expressed on the membrane surface of glioblastoma CSCs, was subsequently conjugated with the PEI- modified SPIO NPs to form anti-CD133 mAb conjugated immunomagnetic nanosensor. The prepared immunomagnetic nanosensor i.e. anti-CD133 mAb-conjugated nanoscale magnetic sensor (mAb-nano-MSN) was biologically assayed with cellular toxicity, cell cycle and specificity, and finally delivered to the targeted CSCs for fluorescence imaging and magnetic resonance imaging (MRI) within human brain glioblastoma CSCs. The results demenstrated that the developed immunomagnetic nanosensor displayed preferable properties such as excellent biocompatibility, non-toxicity and high specificity. The glioblastoma CSCs treated with anti-CD133 mAb-nano-MSN displayed a strong red fluorescence signal and a negative contrast enhancement compared with the cells treated with non-mAb-functionalized magnetic nanopartitles, probably due to efficient endocytosis mediated by anti-CD133 mAb grafted onto the prepared magnetic nanosensor. Therefore, these results indicated the fabricated anti-CD133 mAb-nano-MSN could be used as a promising nanovehicle for molecular imaging for the targeted CSCs in human brain tumor diagnosis and therapy.