title: Nanosphere-based one-step strategy for efficient and nondestructive detection of circulating tumor cells.
abstract: Detecting viable circulating tumor cells (CTCs) without disruption to their functions for in vitro culture and functional study could unravel the biology of metastasis and promote the development of personalized anti-tumor therapies. However, existing CTC detection approaches commonly include CTC isolation and subsequent destructive identification, which damages CTC viability and functions and generates substantial CTC loss. To address the challenge of efficiently detecting viable CTCs for functional study, we develop a nanosphere-based cell-friendly one-step strategy. Immunonanospheres with prominent magnetic/fluorescence properties and extraordinary stability in complex matrices enable simultaneous efficient magnetic capture and specific fluorescence labeling of tumor cells directly in whole blood. The collected cells with fluorescent tags can be reliably identified, free of the tedious and destructive manipulations from conventional CTC identification. Hence, as few as 5 tumor cells in ca. 1mL of whole blood can be efficiently detected via only 20min incubation, and this strategy also shows good reproducibility with the relative standard deviation (RSD) of 8.7%. Moreover, due to the time-saving and gentle processing and the minimum disruption of immunonanospheres to cells, 93.8±0.1% of detected tumor cells retain cell viability and proliferation ability with negligible changes of cell functions, capacitating functional study on cell migration, invasion and glucose uptake. Additionally, this strategy exhibits successful CTC detection in 10/10 peripheral blood samples of cancer patients. Therefore, this nanosphere-based cell-friendly one-step strategy enables viable CTC detection and further functional analyses, which will help to unravel tumor metastasis and guide treatment selection.
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Cong-Ying
authors.initials: CY
authors.lastname: Wen
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Hu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Tang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China; Hubei Cancer Hospital, Wuhan 430079, PR China.
authors.forename: Chu-Bo
authors.initials: CB
authors.lastname: Qi
authors.affiliation: Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Cui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China.
authors.forename: Dai-Wen
authors.initials: DW
authors.lastname: Pang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and Wuhan Institute of Biotechnology, Wuhan University, Wuhan 430072, PR China. Electronic address: zlzhang@whu.edu.cn.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D002469:Cell Separation / Q000379:methods*; D006801:Humans; D054118:Nanospheres / Q000737:chemistry; D009369:Neoplasms / Q000097:blood* / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology
keywords: Cell-friendly; Efficient; Fluorescent nanosphere; Magnetic nanosphere; One-step detection; Viable circulating tumor cell