Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells

Abstract

Current methods for capturing circulating tumor cells (CTCs) are based on the overexpression of cytokeratin (CK) or epithelial cell-adhesion molecule (EpCAM) on cancer cells. However, during the process of metastasis, tumor cells undergo epithelial-to-mesenchymal transition (EMT) that can lead to the loss of CK/EpCAM expression. Therefore, it is vital to develop a capturing technique independent of CK/EpCAM expression on the cancer cell. To develop this technique, it is important to identify common secondary oncogenic markers overexpressed on tumor cells before and after EMT. We analyzed the biomarker expression levels in tumor cells, before and after EMT, and found two common proteinshuman epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) whose levels remained unaffected. So, we synthesized immunomagnetic iron nanocubes covalently conjugated with antibodies of Her2 or EGFR to capture cancer cells irrespective of the EMT status. The nanocubes showed high specificity (6−9-fold) in isolating the cancer cells of interest from a mixture of cells spiked in serum. We characterized the captured cells for identifying their EMT status. Thus, we believe the results presented here would help in the development of novel strategies for capturing both primary and metastatic cancer cells from patients' blood to develop an effective treatment plan.

IONPs-Based Medical Imaging in Cancer Care: Moving Beyond Traditional Diagnosis and Therapeutic Assessment

“… 103 However, for a significant fraction of patients, this system may lead to inherently EpCAM-negative and epithelial-to-mesenchymal transition (EMT) inverted CTCs being ignored. 99 , 100 In order to improve the accuracy of CTCs detection, Chen et al constructed IONPs loaded magnetic immunoliposomes (MIL) linked with one of the four kinds of antibodies (EpCAM, EGFR, HER-2 and mucin-1) ( Figure 6A ). 28 The results indicated that the cumulative CTCs-positive rate was up to 87.5% with four different magnetic nanoparticles, which is much higher than that of any single magnetic nanoparticles and their mixed counterpart ( Figure 6B ).…”

“…Due to its excellent magnetic behavior (>40 emu/g) and easy construction, antibody-modified IONPs can be used for magnetic immunization separation and detection of certain cell populations from biological suspensions. 28,[99][100][101] Briefly, modified IONPs can specifically bind to corresponding receptors on the surface of CTCs and thus isolate CTCs in an external magnetic field. Then, CTCs could be detected through FI or micro-MRI technology.…”

“…Then, CTCs could be detected through FI or micro-MRI technology. [99][100][101] Attributing to simple and gentle processing, 93.8% of the captured CTCs could preserve their viability and function, thereby enabling in vitro culture and further study. 102 A CellSearch system using IONPs linked with anti-epithelial cell adhesion molecule (anti-EpCAM) antibodies has been approved by FDA to diagnose colorectal, prostate and breast cancer.…”

Wastewater Treatment Using Novel Magnetic Nanosponges

“…The suspension was then sonicated for 10 min, and nitrogen gas bubbled on the headspace above the solution with the stopper installed. The presence of MNSs were validated by confirming their magnetic attraction towards a N50-grade neodymium block magnet with a pull force of 250 lb [33]. The suspension was stored at room temperature, and 1 mL was centrifuged at 20,000× g for 20 min and vacuum-dried for 4 h to determine the concentration (mg/mL).…”