title: Improving sensitivity and specificity of capturing and detecting targeted cancer cells with anti-biofouling polymer coated magnetic iron oxide nanoparticles.
abstract: Detecting circulating tumor cells (CTCs) with high sensitivity and specificity is critical to management of metastatic cancers. Although immuno-magnetic technology for in vitro detection of CTCs has shown promising potential for clinical applications, the biofouling effect, i.e., non-specific adhesion of biomolecules and non-cancerous cells in complex biological samples to the surface of a device/probe, can reduce the sensitivity and specificity of cell detection. Reported herein is the application of anti-biofouling polyethylene glycol-block-allyl glycidyl ether copolymer (PEG-b-AGE) coated iron oxide nanoparticles (IONPs) to improve the separation of targeted tumor cells from aqueous phase in an external magnetic field. PEG-b-AGE coated IONPs conjugated with transferrin (Tf) exhibited significant anti-biofouling properties against non-specific protein adsorption and off-target cell uptake, thus substantially enhancing the ability to target and separate transferrin receptor (TfR) over-expressed D556 medulloblastoma cells. Tf conjugated PEG-b-AGE coated IONPs exhibited a high capture rate of targeted tumor cells (D556 medulloblastoma cell) in cell media (58.7±6.4%) when separating 100 targeted tumor cells from 1×105non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads®).
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Run
authors.initials: R
authors.lastname: Lin
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Yuancheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Tobey
authors.initials: T
authors.lastname: MacDonald
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: James
authors.initials: J
authors.lastname: Provenzale
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Radiology, The Medical College of Southeastern University, Nanjing, Jiangsu, China.
authors.forename: Xingui
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Wang
authors.affiliation: Ocean NanoTech, LLC, San Diego, CA 20046, USA.
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Wang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: hmao@emory.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
mesh_terms: D000327:Adsorption; D000818:Animals; D057219:Biofouling; D015415:Biomarkers / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008027:Light; D008264:Macrophages / Q000378:metabolism; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011990:Receptors, Transferrin / Q000737:chemistry; D012680:Sensitivity and Specificity; D013499:Surface Properties; D014168:Transferrin / Q000737:chemistry
chemical_list: D015415:Biomarkers; D005290:Ferric Compounds; D008024:Ligands; D058185:Magnetite Nanoparticles; D011108:Polymers; D011990:Receptors, Transferrin; D014168:Transferrin; C000499:ferric oxide; D011092:Polyethylene Glycols
keywords: Anti-biofouling; Cell separation; Circulating tumor cells; Magnetic nanoparticles; Targeting