Multifunctional magnetic nanowires: A novel breakthrough for ultrasensitive detection and isolation of rare cancer cells from non-metastatic early breast cancer patients using small volumes of blood

Hong, Won‐Kee; Lee, Sooyeon; Chang, Hee Jin; Lee, Eun Sook; Cho, Youngnam

doi:10.1016/j.biomaterials.2016.08.020

Cited by 63 publications

(40 citation statements)

References 26 publications

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“…First, we optimized and evaluated the performance of the Ab cocktail/mPpy NW using cell lines (i.e., EpCAM-positive MCF7 cells and EpCAM-negative MIA PaCa-2 cells) that were spiked ex vivo into PBS or whole blood, and we achieved a capture yield of ~90% (Figure S4 ). Indeed, as demonstrated in a previous study, the use of five different types of antibodies resulted in significantly higher isolation efficiency regardless of the EpCAM expression levels in tumor cells 21 . As with cfDNA extraction, the ability of the NWs to capture CTCs was mainly attributed to their long and thin morphology, which provides the structural and chemical cues required for CTC recovery efficiency: the elongated structure of the NWs not only significantly decreases the inherent steric hindrance, but also increases the duration and surface area of contact with cancer cells as the NWs wrap themselves around the cells.…”

Section: Resultssupporting

confidence: 52%

“…In our previous studies, we developed an electroactive conducting polymer platform (i.e., polypyrrole (Ppy)), where reversible transition in the oxidized and reduced states of the polymeric chains was employed for ultrasensitive isolation of cfDNA and CTCs from blood samples of patients with cancer 18 - 20 . In more recent studies, we presented a strategy for extracting CTCs using magnetic nanowires (NWs) and demonstrated the excellent performance of these NWs in processing and analyzing CTCs from the blood of patients, even in early-stage non-metastatic breast cancer 21 . By combining two types of epithelial and mesenchymal markers (i.e., EpCAM, epidermal growth factor receptor (EGFR), TROP-2, vimentin, and N-cadherin) on the NW surface, we not only significantly increased the likelihood of capturing CTCs with high phenotypic variation but also minimized the loss of EpCAM-negative CTCs during the process.…”

Section: Introductionmentioning

confidence: 99%

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Magnetic Nanowire Networks for Dual-Isolation and Detection of Tumor-Associated Circulating Biomarkers

et al. 2018

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Purpose: Recent developments in genomic and molecular methods have revolutionized the range of utilities of tumor-associated circulating biomarkers in both basic and clinical research. Herein, we present a novel approach for ultrasensitive extraction of cfDNA and CTCs, at high yield and purity, via the formation of magnetic nanowire networks.Materials and Methods: We fabricated and characterized biotinylated cationic polyethylenimine and biotinylated antibody cocktail-conjugated magnetic polypyrrole NWs (PEI/mPpy NW and Ab cocktail/mPpy NW, respectively). We applied these NWs to the extraction of cfDNA and CTC from the blood of 14 patients with lung cancer. We demonstrated reliable detection of EGFR mutations based on digital droplet PCR analysis of cfDNA and CTC DNA from patients with lung cancer.Results: The NW networks confined with a high density of magnetic nanoparticles exhibited superior saturation magnetization, which enabled rapid and high-yield capture whilst avoiding or minimizing damage and loss. The NW networks enabled the co-isolation of CTCs and cfDNA of high quality and sufficient quantities, thus allowing the amplification of rare and low-prevalence cancer-related mutations.Conclusion: The simple, versatile, and highly efficient nanowire network tool allows sensitive and robust assessment of clinical samples.

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Section: Resultssupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Magnetic Nanowire Networks for Dual-Isolation and Detection of Tumor-Associated Circulating Biomarkers

et al. 2018

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“…Thus, a combination of both EpCAM- and non-EpCAM-based CTC technologies seems to be needed in order to better assess the presence of CTCs in patients with SCLC and to evaluate their biological and clinical relevance. It should be noted that new and promising methodologies have also been developed for the detection of CTCs based on nanoparticles575859606162; however, these methods have serious limitations, such as the higher cost and the requirement of special equipment compared to the simple immunofluorescence staining.…”

Section: Discussionmentioning

confidence: 99%

TTF-1- and/or CD56-positive Circulating Tumor Cells in patients with small cell lung cancer (SCLC)

Messaritakis

Stoltidis

Κotsakis

et al. 2017

Sci Rep

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The aim of the study was to evaluate the phenotypic CTCs heterogeneity (TTF-1+ and/or CD56+) in SCLC patients and correlate it with the CellSearch. Peripheral blood was obtained from 108 consecutive patients. CTCs were detected by CellSearch and double-immunofluorescence using anti-CD45, anti-TTF-1 and anti-CD56 antibodies. Before chemotherapy TTF-1+/CD45−, CD56+/CD45− and TTF-1+/CD56+ CTCs were detected in 66(61.1%), 55(50.9%) and 46(42.6%) patients, respectively; 60.2% of patients were CellSearch+. Among the 22 patients with 0 CTCs/7.5 ml on CellSearch, TTF-1+/CD45−, CD56+/CD45− and TTF-1+/CD56+ CTCs were detected in 8(36.4%), 6(27.3) and 6(27.3%) patients, respectively; no CK+/EpCAM+ or TTF1+/EpCAM+ CTCs were detected in these patients. One-chemotherapy cycle decreased both the number of positive patients (p < 0.001) and their CTC number (p < 0.001), irrespectively of their phenotype and the detection method. The incidence and number of the different CTC subpopulations on PD, was significantly increased at their baseline levels. Multivariate analysis revealed that the increased number of CTCs at baseline and on PD were significantly associated with decreased PFS (p = 0.048) and OS (p = 0.041), respectively. There is an important CTC heterogeneity in such patients according to the expression of TTF-1 and CD56 which could detect EpCAM− CTC subpopulations and, thus, undetectable by CellSearch. These CTC subpopulations are dynamically correlated with treatment efficacy and disease-progression.

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“…31,32 Furthermore, the MNWs have shown a high internalization by cells in comparison to other magnetic nanoparticles, such as IONs, improving the enrichment and multiplexing yield. 26,28,33 As a consequence, MNWs have recently attracted attention as enrichment agents for studying breast and lung cancers, 34,35 CTCs, 36 and leukemia. 37 Regardless of the tremendous opportunities for MNWs, they have not been used as self-standing biomarkers for multiplexing applications up to date due to three major drawbacks.…”

Section: Introductionmentioning

confidence: 99%

Projection method as a probe for multiplexing/demultiplexing of magnetically enriched biological tissues

Kouhpanji

Stadler

2020

RSC Adv.

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Multifunctional magnetic nanowires: A novel breakthrough for ultrasensitive detection and isolation of rare cancer cells from non-metastatic early breast cancer patients using small volumes of blood

Cited by 63 publications

References 26 publications

Magnetic Nanowire Networks for Dual-Isolation and Detection of Tumor-Associated Circulating Biomarkers

Magnetic Nanowire Networks for Dual-Isolation and Detection of Tumor-Associated Circulating Biomarkers

TTF-1- and/or CD56-positive Circulating Tumor Cells in patients with small cell lung cancer (SCLC)

Projection method as a probe for multiplexing/demultiplexing of magnetically enriched biological tissues

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