title: Programming thermoresponsiveness of NanoVelcro substrates enables effective purification of circulating tumor cells in lung cancer patients.
abstract: Unlike tumor biopsies that can be constrained by problems such as sampling bias, circulating tumor cells (CTCs) are regarded as the "liquid biopsy" of the tumor, providing convenient access to all disease sites, including primary tumor and fatal metastases. Although enumerating CTCs is of prognostic significance in solid tumors, it is conceivable that performing molecular and functional analyses on CTCs will reveal much significant insight into tumor biology to guide proper therapeutic intervention. We developed the Thermoresponsive NanoVelcro CTC purification system that can be digitally programmed to achieve an optimal performance for purifying CTCs from non-small cell lung cancer (NSCLC) patients. The performance of this unique CTC purification system was optimized by systematically modulating surface chemistry, flow rates, and heating/cooling cycles. By applying a physiologically endurable stimulation (i.e., temperature between 4 and 37 °C), the mild operational parameters allow minimum disruption to CTCs' viability and molecular integrity. Subsequently, we were able to successfully demonstrate culture expansion and mutational analysis of the CTCs purified by this CTC purification system. Most excitingly, we adopted the combined use of the Thermoresponsive NanoVelcro system with downstream mutational analysis to monitor the disease evolution of an index NSCLC patient, highlighting its translational value in managing NSCLC.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University , Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Zunfu
authors.initials: Z
authors.lastname: Ke
authors.forename: Millicent
authors.initials: M
authors.lastname: Lin
authors.forename: Jie-Fu
authors.initials: JF
authors.lastname: Chen
authors.forename: Jin-Sil
authors.initials: JS
authors.lastname: Choi
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Anna
authors.initials: A
authors.lastname: Fong
authors.forename: An-Jou
authors.initials: AJ
authors.lastname: Liang
authors.forename: Shang-Fu
authors.initials: SF
authors.lastname: Chen
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Li
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Fang
authors.forename: Pingshan
authors.initials: P
authors.lastname: Zhang
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Garcia
authors.forename: Tom
authors.initials: T
authors.lastname: Lee
authors.forename: Min
authors.initials: M
authors.lastname: Song
authors.forename: Hsing-An
authors.initials: HA
authors.lastname: Lin
authors.forename: Haichao
authors.initials: H
authors.lastname: Zhao
authors.forename: Shyh-Chyang
authors.initials: SC
authors.lastname: Luo
authors.forename: Shuang
authors.initials: S
authors.lastname: Hou
authors.forename: Hsiao-Hua
authors.initials: HH
authors.lastname: Yu
authors.forename: Hsian-Rong
authors.initials: HR
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D049329:Nanostructures / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D013696:Temperature
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule
keywords: cancer diagnosis; circulating tumor cells; nanostructured materials; non-small cell lung cancer; thermoresponsive polymer