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.
Bibliographical noteFunding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Hong and A.Z. Wang are co-founders of Capio Biosciences, Inc., a biotech startup that is commercializing CapioCyte? CTC technology. M.J. Poellmann is an employee of Capio Biosciences.T. Zhang has received research funding (to Duke) from Abbvie, Acerta, Janssen, Merck, Merrimack, Novartis, OmniSeq, Pfizer, and PGDx; speaking fees from Exelixis, Genentech, Roche, Sanofi Aventis, and Genomic Health; and has consulted for AstraZeneca, Bristol-Myers Squibb, Foundation Medicine, Janssen, Pfizer, Pharmacyclics, Amgen, and Sanofi Aventis. Stock ownership/employment (spouse) from Capio Biosciences.This study was partially supported by DRP program of the Wisconsin Head & Neck Cancer SPORE Grant (P50-DE026787) and by Sponsored Research Program (SRP) from Capio Biosciences, Inc.
This study was partially supported by DRP program of the Wisconsin Head & Neck Cancer SPORE Grant (P50-DE026787) and by Sponsored Research Program (SRP) from Capio Biosciences, Inc .
© 2020 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Biomedical Engineering