Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Lee H

PROVIDER: S-EPMC5743563 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

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

Lee HyungJae H Choi Mihye M Lim Jiyun J Jo Minkyung M Han Ji-Youn JY Kim Tae Min TM Cho Youngnam Y

Theranostics 20180101 2

<b>Purpose:</b> 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. <b>Materials and Methods:</b> We fabricated and characterized biotinylated cationic polyethylenimine and biotinylated antibody cocktail-conjugated m ...[more]

PMID: 29290823

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Project description:Circulating tumor cells (CTCs) are cancer cells that break away from either a primary tumor or a metastatic site and circulate in the peripheral blood as the cellular origin of metastasis. With their role as a "tumor liquid biopsy", CTCs provide convenient access to all disease sites, including that of the primary tumor and the site of fatal metastases. It is conceivable that detecting and analyzing CTCs will provide insightful information in assessing the disease status without the flaws and limitations encountered in performing conventional tumor biopsies. However, identifying CTCs in patient blood samples is technically challenging due to the extremely low abundance of CTCs among a large number of hematologic cells. To address this unmet need, there have been significant research endeavors, especially in the fields of chemistry, materials science, and bioengineering, devoted to developing CTC detection, isolation, and characterization technologies. Inspired by the nanoscale interactions observed in the tissue microenvironment, our research team at UCLA pioneered a unique concept of "NanoVelcro" cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with high efficiency. The working mechanism of NanoVelcro cell-affinity substrates mimics that of Velcro: when the two fabric strips of a Velcro fastener are pressed together, tangling between the hairy surfaces on two strips leads to strong binding. Through continuous evolution, three generations (gens) of NanoVelcro CTC chips have been established to achieve different clinical utilities. The first-gen NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side analytical validation studies using clinical blood samples suggested that the sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved CellSearch. In conjunction with the use of the laser microdissection (LMD) technique, second-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation. The individually isolated CTCs can be subjected to single-CTC genotyping (e.g., Sanger sequencing and next-generation sequencing, NGS) to verify the CTC's role as tumor liquid biopsy. Created by grafting of thermoresponsive polymer brushes onto SiNS, third-gen NanoVelcro chips (i.e., Thermoresponsive NanoVelcro) have demonstrated the capture and release of CTCs at 37 and 4 °C, respectively. The temperature-dependent conformational changes of polymer brushes can effectively alter the accessibility of the capture agent on SiNS, allowing for rapid CTC purification with desired viability and molecular integrity. This Account summarizes the continuous evolution of NanoVelcro CTC assays from the emergence of the original idea all the way to their applications in cancer research. We envision that NanoVelcro CTC assays will lead the way for powerful and cost-efficient diagnostic platforms for researchers to better understand underlying disease mechanisms and for physicians to monitor real-time disease progression.

Dataset Information

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

Publications

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

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