Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells

TL;DR

This study develops iron nanocubes conjugated with Her2 or EGFR antibodies to capture circulating tumor cells regardless of EMT status, aiding in better detection and treatment of metastatic cancer.

Contribution

It introduces a novel magnetic nanocube-based method targeting Her2 and EGFR for CK/EpCAM-independent cancer cell capture.

Findings

High specificity (6-9 fold) in isolating cancer cells from serum.

Effective capture of cells before and after EMT.

Potential for improved metastatic cancer detection.

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 to 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.