Capture of Heterogeneous Circulating Tumor Cells in Colorectal Cancer Patients on an Immunomagnetic and Anti-Nonspecific Adsorption Platform

Abstract

Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial−mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe 3 O 4 @SiO 2 @PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe 3 O 4 @SiO 2 , which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe 3 O 4 @SiO 2 improved the antinonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe 3 O 4 @SiO 2 @ PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.

Recent progress of nanostructure-based enrichment of circulating tumor cells and downstream analysis

“…Based on the immunomagnetic platform Fe 3 O 4 @SiO 2 @PTMAO@aptamer, Li et al detected the number of epithelial CTC (E-CTC), stromal CTC (M-CTC) and mixed (epithelial and stromal) CTC (EM-CTC) in blood samples of patients with colorectal cancer, and analyzed the correlation between different phenotypes of CTCs and clinical information of CRC patients. 28 The changes of the proportion of heterogeneous CTC in 40 patients with different stages of colorectal cancer before and after operation showed that the number and proportion of E-CTC or M-CTC was significantly lower than that of EM-CTC and M-CTC. This was positively correlated with the metastasis of colorectal cancer and the effect of operation and chemotherapy in patients with CRC.…”

“…70 Li et al designed a new type of anti-non-specific adsorption immunomagnetic platform Fe 3 O 4 @SiO 2 @PTMAO@aptamer, which can efficiently capture different phenotypes of CTCs in 10 min, and briefly analyzed the relationship between different phenotypes of CTCs and the progression, diagnosis, surgery and chemotherapy of colorectal cancer (CRC) patients. 28 In addition, the team designed double aptamer (EpCAM and PTK7)-modified immunomagnetic Fe 3 O 4 particles for the effective capture and downstream analysis of heterogeneous CTCs in patients with gastric cancer (Fig. 5C ).…”

Metabolic Glycoengineering-Programmed Nondestructive Capture of Circulating Tumor Cells

“…Circulating tumor cells (CTCs) are the “seeds” of malignant tumor metastasis that detach from the primary tumor, breach the basement membrane, and enter the bloodstream or lymphatic fluid. , They are widely observed in various types of tumors. Therefore, research on the nondestructive capture of CTCs holds clinical value in minimally invasive tumor diagnosis, disease monitoring, prognosis assessment, drug guidance, and even drug efficacy evaluation. − Among these, nondestructive CTC capture is the most critical prerequisite. − Currently, CTC capture techniques have been extensively studied. − Some aim to utilize CTC-specific membrane protein biomarkers, while others aim to exploit the unique physical properties of CTCs, such as membrane potential. , However, unfortunately, strategies for CTC capture that maintain high specificity, sensitivity, and universality remain limited . Specifically, membrane protein biomarkers undoubtedly provide targets for highly specific CTC capture.…”

“…7−9 Currently, CTC capture techniques have been extensively studied. 10−14 Some aim to utilize CTC-specific membrane protein biomarkers, 11 while others aim to exploit the unique physical properties of CTCs, such as membrane potential. 15,16 However, unfortunately, strategies for CTC capture that maintain high specificity, sensitivity, and universality remain limited.…”

Digital Circulating Tumor Cells Quantification

“…Since the CTCs are from the tumor tissue, they usually carry different characteristics from the blood cells. Various strategies have been applied to enrich the CTCs by using these characteristics, − including cell density, size, etc., and those by taking advantage of antibodies, , aptamers, − or peptides , to capture the CTCs based on the specific biomarkers on the surface of it. To improve the enrichment performance, microfluidics or functional nanomaterials are especially favored. − After the enrichment, immunodetection or gene-related strategies are introduced to identify and analyze the cells further.…”