title: In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells.
abstract: The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths. Detecting circulating tumour cells -- a common marker for the development of metastasis -- is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans.
authors.affiliation: Phillips Classic Laser and Nanomedicine Laboratories, Winthrop P Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
authors.forename: Ekaterina I
authors.initials: EI
authors.lastname: Galanzha
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Shashkov
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelly
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Kim
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zharov
mesh_terms: D000162:Acoustics; D000818:Animals; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer / Q000379:methods*; D006801:Humans; D008027:Light; D008280:Magnetics / Q000379:methods*; D051379:Mice; D018716:Molecular Mimicry; D053758:Nanoparticles; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000473:pathology; D009369:Neoplasms / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D012212:Rheology