TY - JOUR
T1 - Surface engineering for efficient capture of circulating tumor cells in renal cell carcinoma
T2 - From nanoscale analysis to clinical application
AU - Bu, Jiyoon
AU - Nair, Ashita
AU - Kubiatowicz, Luke J.
AU - Poellmann, Michael J.
AU - Jeong, Woo jin
AU - Reyes-Martinez, Marco
AU - Armstrong, Andrew J.
AU - George, Daniel J.
AU - Wang, Andrew Z.
AU - Zhang, Tian
AU - Hong, Seungpyo
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/8/15
Y1 - 2020/8/15
N2 - Sensitive detection of circulating tumor cells (CTCs) from patients' peripheral blood facilitates on-demand monitoring of tumor progression. However, clinically significant capture of renal cell carcinoma CTCs (RCC-CTCs) remains elusive due to their heterogenous surface receptor expression. Herein, a novel capture platform is developed to detect RCC-CTCs through integration of dendrimer-mediated multivalent binding, a mixture of antibodies, and biomimetic cell rolling. The nanoscale binding kinetics measured using atomic force microscopy reveal that dendrimer-coated surfaces exhibit an order of magnitude enhancement in off-rate kinetics compared to surface without dendrimers, which translated into cell capture improvements by ~60%. Selectin-induced cell rolling facilitates surface recruitment of cancer cells, further improving cancer cell capture by up to 1.7-fold. Lastly, an antibody cocktail targeting four RCC-CTC surface receptors, which included epithelial cell adhesion molecule (EpCAM), carbonic anhydrase IX (CA9), epidermal growth factor receptor (EGFR), and hepatocyte growth factor receptor (c-Met), improves the capture of RCC cells by up to 80%. The optimal surface configuration outperforms the conventional assay solely relying on EpCAM, as demonstrated by detecting significantly more CTCs in patients’ samples (9.8 ± 5.1 vs. 1.8 ± 2.0 CTCs mL-1). These results demonstrate that the newly engineered capture platform effectively detects RCC-CTCs for their potential use as tumor biomarkers.
AB - Sensitive detection of circulating tumor cells (CTCs) from patients' peripheral blood facilitates on-demand monitoring of tumor progression. However, clinically significant capture of renal cell carcinoma CTCs (RCC-CTCs) remains elusive due to their heterogenous surface receptor expression. Herein, a novel capture platform is developed to detect RCC-CTCs through integration of dendrimer-mediated multivalent binding, a mixture of antibodies, and biomimetic cell rolling. The nanoscale binding kinetics measured using atomic force microscopy reveal that dendrimer-coated surfaces exhibit an order of magnitude enhancement in off-rate kinetics compared to surface without dendrimers, which translated into cell capture improvements by ~60%. Selectin-induced cell rolling facilitates surface recruitment of cancer cells, further improving cancer cell capture by up to 1.7-fold. Lastly, an antibody cocktail targeting four RCC-CTC surface receptors, which included epithelial cell adhesion molecule (EpCAM), carbonic anhydrase IX (CA9), epidermal growth factor receptor (EGFR), and hepatocyte growth factor receptor (c-Met), improves the capture of RCC cells by up to 80%. The optimal surface configuration outperforms the conventional assay solely relying on EpCAM, as demonstrated by detecting significantly more CTCs in patients’ samples (9.8 ± 5.1 vs. 1.8 ± 2.0 CTCs mL-1). These results demonstrate that the newly engineered capture platform effectively detects RCC-CTCs for their potential use as tumor biomarkers.
KW - Biomimetic cell rolling
KW - Circulating tumor cells
KW - Dendrimer-mediated multivalent binding effect
KW - Liquid biopsy
KW - Renal cell carcinoma
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UR - http://www.scopus.com/inward/citedby.url?scp=85084190522&partnerID=8YFLogxK
U2 - 10.1016/j.bios.2020.112250
DO - 10.1016/j.bios.2020.112250
M3 - Article
C2 - 32392161
AN - SCOPUS:85084190522
SN - 0956-5663
VL - 162
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
M1 - 112250
ER -