Degradable Zinc-Phosphate-Based Hierarchical Nanosubstrates for Capture and Release of Circulating Tumor Cells.
Circulating tumor cells (CTCs) play a significant role in cancer diagnosis and personalized therapy, and it is still a significant challenge to efficiently capture and gently release CTCs from clinical samples for downstream manipulation and molecular analysis. Many CTC devices incorporating various nanostructures have been developed for CTC isolation with sufficient capture efficiency, however, fabricating such nanostructured substrates often requires elaborate design and complicated procedures. Here we fabricate a degradable zinc-phosphate-based hierarchical nanosubstrate (HZnPNS), and we demonstrate its excellent CTC-capture performance along with effective cell-release capability for downstream molecular analysis. This transparent hierarchical architecture prepared by a low-temperature hydrothermal method, enables substantially enhanced capture efficiency and convenient imaging. Biocompatible sodium citrate could rapidly dissolve the architecture at room temperature, allowing that 88 ± 4% of captured cells are gently released with a high viability of 92 ± 1%. Furthermore, antiepithelial cell adhesion molecule antibody functionalized HZnPNS (anti-EpCAM/HZnPNS) was successfully applied to isolate CTCs from whole blood samples of cancer patients, as well as release CTCs for global DNA methylation analysis, indicating it will serve as a simple and reliable alternative platform for CTC detection.
College of Chemistry and Molecular Sciences, The Institute for Advanced Studies of Wuhan University, Wuhan University , Wuhan 430072, China.
Shan
S
Guo
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Jiaquan
J
Xu
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Min
M
Xie
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Wei
W
Huang
Zhongnan Hospital, Wuhan University , Wuhan 430072, China.
Erfeng
E
Yuan
Renmin Hospital of Wuhan University , Wuhan 430060, China.
Ya
Y
Liu
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Liping
L
Fan
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Shibo
S
Cheng
Zhongnan Hospital, Wuhan University , Wuhan 430072, China.
Songmei
S
Liu
Zhongnan Hospital, Wuhan University , Wuhan 430072, China.
Fubing
F
Wang
College of Chemistry and Molecular Sciences, The Institute for Advanced Studies of Wuhan University, Wuhan University , Wuhan 430072, China.
Bifeng
B
Yuan
Renmin Hospital of Wuhan University , Wuhan 430060, China.
Weiguo
W
Dong
State Key Laboratory of Virology, Department of Immunology, School of Medicine, Wuhan University , Wuhan 430072, China.
Xiaolian
X
Zhang
Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
Weihua
W
Huang
College of Chemistry and Molecular Sciences, The Institute for Advanced Studies of Wuhan University, Wuhan University , Wuhan 430072, China.
Xiang
X
Zhou
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D006801:Humans; D049329:Nanostructures / Q000737:chemistry*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry*; D017967:Zinc Compounds / Q000737:chemistry*
D015815:Cell Adhesion Molecules; D010710:Phosphates; D017967:Zinc Compounds; C043952:zinc phosphate
capture; circulating tumor cells; degradable; hierarchical nanosubstrates; molecular analysis; release; zinc phosphate