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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.

SUBMITTER: Suresh D

PROVIDER: S-EPMC7513327 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells.

Suresh Dhananjay D Ghoshdastidar Shreya S Gangula Abilash A Mukherjee Soumavo S Upendran Anandhi A Kannan Raghuraman R

ACS omega 20200909 37

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 com ...[more]

PMID: 32984691

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Project description:Here, we report a nanoplatform based on iron oxide nanocubes (IONCs) coated with a bioresorbable polymer that, upon exposure to lytic enzymes, can be disassembled increasing the heat performances in comparison with the initial clusters. We have developed two-dimensional (2D) clusters by exploiting benchmark IONCs as heat mediators for magnetic hyperthermia and a polyhydroxyalkanoate (PHA) copolymer, a biodegradable polymer produced by bacteria that can be digested by intracellular esterase enzymes. The comparison of magnetic heat performance of the 2D assemblies with 3D centrosymmetrical assemblies or single IONCs emphasizes the benefit of the 2D assembly. Moreover, the heat losses of 2D assemblies dispersed in water are better than the 3D assemblies but worse than for single nanocubes. On the other hand, when the 2D magnetic beads (2D-MNBs) are incubated with the esterase enzyme at a physiological temperature, their magnetic heat performances began to progressively increase. After 2 h of incubation, specific absorption rate values of the 2D assembly double the ones of individually coated nanocubes. Such an increase can be mainly correlated to the splitting of the 2D-MNBs into smaller size clusters with a chain-like configuration containing few nanocubes. Moreover, 2D-MNBs exhibited nonvariable heat performances even after intentionally inducing their aggregation. Magnetophoresis measurements indicate a comparable response of 3D and 2D clusters to external magnets (0.3 T) that is by far faster than that of single nanocubes. This feature is crucial for a physical accumulation of magnetic materials in the presence of magnetic field gradients. This system is the first example of a nanoplatform that, upon exposure to lytic enzymes, such as those present in a tumor environment, can be disassembled from the initial 2D-MNB organization to chain-like assemblies with clear improvement of the heat magnetic losses resulting in better heat dissipation performances. The potential application of 2D nanoassemblies based on the cleavable PHAs for preserving their magnetic losses inside cells will benefit hyperthermia therapies mediated by magnetic nanoparticles under alternating magnetic fields.

Dataset Information

Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells.

Publications

Magnetic Iron Nanocubes Effectively Capture Epithelial and Mesenchymal Cancer Cells.

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