Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging

Abstract

Background The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells. Materials and methods Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N -ethyl- N -nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production. Results USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab. Conclusion Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors.

Evaluation of Chitosan Derivative Microparticles Encapsulating Superparamagnetic Iron Oxide and Doxorubicin as a pH-Sensitive Delivery Carrier in Hepatic Carcinoma Treatment: An in vitro Comparison Study

“…All images were obtained as follows: a sagittal two-dimensional fast spin echo (FSE) sequence (echo time/repetition time, 99/6000; number of excitations, 8; echo train length, 32), 192 × 192 matrix, field of view of 100 × 100 mm, and section thickness of 2 mm. The experimental parameters were referred to details provided in previous studies (Chen et al, 2015 ; Tang et al, 2017 ).…”

Lineage Tracing and Molecular Real-Time Imaging of Cancer Stem Cells

“…64 Cu-YY146 can be used to specifically detect the orthotopic and subcutaneous brain tumors using PET. In addition, YY146 can detect CD146 + CSC in other tumor tissues, such as ovary, lung, liver, and stomach [ 18 ].…”

“…Radioactive bioactive molecules such as 125 I, 64 Cu, 68 Ga, and 18 F were used for PET imaging. Chen et al used 125 I-labeled ANC9C5, an anti-human CD133 antibody to investigate the in vivo radionuclide imaging potential of CSC in colon carcinoma xenografts [ 18 ]. The results showed that CD133 immunohistochemistry expression was overlapped with intra-tumoral distribution of 125 I-labeled ANC9C5 depicted on autoradiography in many areas.…”

Potential applications and human biosafety of nanomaterials used in nanomedicine

“…NPs also have higher hardness, higher plasticity, higher specific heat and thermal expansion, higher conductivity, higher diffusivity, lower sintering temperature and sintering shrinkage than large ones (Zhang et al, 2013a). Other properties unique among NPs include surface plasmon resonance in some metal particles and superparamagnetism in magnetic materials (Chen et al, 2015d; Estelrich et al, 2015; Hussein-Al-Ali et al, 2014; Skopalik et al., 2014), which makes them desirable as a magnetic-targeting tool for medical applications.…”