Improving sensitivity and specificity of capturing and detecting targeted cancer cells with anti-biofouling polymer coated magnetic iron oxide nanoparticles

• Type of Material: Article
• Authors: Run Lin, Emory University; Yuancheng Li, Emory University; Tobey MacDonald, Emory University; Hui Wu, Emory University; James Provenzale, Duke University; Xingui Peng, Emory University; Jing Huang, Emory University; Liya Wang, Emory University; Andrew Y. Wang, Ocean NanoTech, LLC; Jianyong Yang, Sun Yat-sen University; Hui Mao, Emory University
• Language: English
• Date: 2017-02-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier B.V.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.colsurfb.2016.10.026
• Title of Journal or Parent Work: Colloids and Surfaces B: Biointerfaces
• ISSN: 0927-7765
• Volume: 150
• Start Page: 261
• End Page: 270
• Grant/Funding Information: This work is supported in parts by NIH R01CA154846-02 (HM and LY), NCI’s Cancer Nanotechnology Platform Project (CNPP) grant U01CA151810-02 (HM and LY), a seed grant from the Center for Pediatric Nanomedicine of Children’s Healthcare of Atlanta (HM and TM), and Oversea Study Program of Guangzhou Elite Project (GEP, 11YB18) (RL).
• Keywords: Biophysics; BREAST-CANCER; Circulating tumor cells; ENRICHMENT; LEUKEMIA B-CELLS; TRANSFERRIN; Physical Sciences; RESISTANT PROSTATE-CANCER; Anti-biofouling; Life Sciences & Biomedicine; IN-VITRO; RECEPTOR; Science & Technology; Chemistry; Chemistry, Physical; Materials Science, Biomaterials; Targeting; SEPARATION; Technology; Cell separation; Magnetic nanoparticles; CIRCULATING TUMOR-CELLS; Materials Science; PERIPHERAL-BLOOD
• Research Categories: Health Sciences, Radiology

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 m edia (58.7 ± 6.4%) when separating 100 targeted tumor cells from 1 × 10 5 non-targeted cells and 41 targeted tumor cells from 100 D556 medulloblastoma cells spiked into 1 mL blood. It is demonstrated that developed nanoparticle has higher efficiency in capturing targeted cells than widely used micron-sized particles (i.e., Dynabeads ® ).