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      Emerging Role of Nanomaterials in Circulating Tumor Cell Isolation and Analysis

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          Abstract

          Circulating tumor cells (CTCs) are low frequency cells found in the bloodstream after having been shed from a primary tumor. These cells are research targets because of the information they may potentially provide about both an individual cancer as well as the mechanisms through which cancer spreads in the process of metastasis. Established technologies exist for CTC isolation, but the recent progress and future of this field lie in nanomaterials. In this review, we provide perspective into historical CTC capture as well as current research being conducted, emphasizing the significance of the materials being used to fabricate these devices. The modern investigation into CTCs initially featured techniques that have since been commercialized. A major innovation in the field was the development of a microfluidic capture device, first fabricated in silicon and followed up with glass and thermopolymer devices. We then specifically highlight the technologies incorporating magnetic nanoparticles, carbon nanotubes, nanowires, nanopillars, nanofibers, and nanoroughened surfaces, graphene oxide and their fabrication methods. The nanoscale provides a new set of tools that has the potential to overcome current limitations associated with CTC capture and analysis. We believe the current trajectory of the field is in the direction of nanomaterials, allowing the improvements necessary to further CTC research.

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          Most cited references80

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          Preparation and characterization of graphene oxide paper.

          Free-standing paper-like or foil-like materials are an integral part of our technological society. Their uses include protective layers, chemical filters, components of electrical batteries or supercapacitors, adhesive layers, electronic or optoelectronic components, and molecular storage. Inorganic 'paper-like' materials based on nanoscale components such as exfoliated vermiculite or mica platelets have been intensively studied and commercialized as protective coatings, high-temperature binders, dielectric barriers and gas-impermeable membranes. Carbon-based flexible graphite foils composed of stacked platelets of expanded graphite have long been used in packing and gasketing applications because of their chemical resistivity against most media, superior sealability over a wide temperature range, and impermeability to fluids. The discovery of carbon nanotubes brought about bucky paper, which displays excellent mechanical and electrical properties that make it potentially suitable for fuel cell and structural composite applications. Here we report the preparation and characterization of graphene oxide paper, a free-standing carbon-based membrane material made by flow-directed assembly of individual graphene oxide sheets. This new material outperforms many other paper-like materials in stiffness and strength. Its combination of macroscopic flexibility and stiffness is a result of a unique interlocking-tile arrangement of the nanoscale graphene oxide sheets.
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            Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.

            The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas. The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors. Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers. The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
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              PEGylated nanographene oxide for delivery of water-insoluble cancer drugs.

              It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nanographene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analogue, SN38, noncovalently via pi-pi stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA-approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.
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                Author and article information

                Journal
                ACS Nano
                ACS Nano
                nn
                ancac3
                ACS Nano
                American Chemical Society
                1936-0851
                1936-086X
                27 February 2015
                27 February 2014
                25 March 2014
                : 8
                : 3
                : 1995-2017
                Affiliations
                [1]Department of Chemical Engineering and Biomedical Engineering, Biointerfaces Institute, Translational Oncology Program, University of Michigan , Ann Arbor, Michigan 48109, United States
                Author notes
                [* ]Address correspondence to snagrath@ 123456umich.edu .
                Article
                10.1021/nn5004277
                4004319
                24601556
                129aace2-11ad-4f24-b7d2-17de47915083
                Copyright © 2014 American Chemical Society
                History
                : 22 January 2014
                : 27 February 2014
                Funding
                National Institutes of Health, United States
                Categories
                Review
                Custom metadata
                nn5004277
                nn-2014-004277

                Nanotechnology
                nanomaterial,circulating tumor cell (ctc),magnetic nanoparticle (mnp),carbon nanotube,nanopillar,nanowire,nanofiber,nanoroughened surface,graphene oxide

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