Surfactant functionalization induces robust, differential adhesion of tumor cells and blood cells to charged nanotube-coated biomaterials under flow.
The metastatic spread of cancer cells from the primary tumor to distant sites leads to a poor prognosis in cancers originating from multiple organs. Increasing evidence has linked selectin-based adhesion between circulating tumor cells (CTCs) and endothelial cells of the microvasculature to metastatic dissemination, in a manner similar to leukocyte adhesion during inflammation. Functionalized biomaterial surfaces hold promise as a diagnostic tool to separate CTCs and potentially treat metastasis, utilizing antibody and selectin-mediated interactions for cell capture under flow. However, capture at high purity levels is challenged by the fact that CTCs and leukocytes both possess selectin ligands. Here, a straightforward technique to functionalize and alter the charge of naturally occurring halloysite nanotubes using surfactants is reported to induce robust, differential adhesion of tumor cells and blood cells to nanotube-coated surfaces under flow. Negatively charged sodium dodecanoate-functionalized nanotubes simultaneously enhanced tumor cell capture while negating leukocyte adhesion, both in the presence and absence of adhesion proteins, and can be utilized to isolate circulating tumor cells regardless of biomarker expression. Conversely, diminishing nanotube charge via functionalization with decyltrimethylammonium bromide both abolished tumor cell capture while promoting leukocyte adhesion.
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; David H. Koch Institute for Integrative Cancer Research, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Michael J
MJ
Mitchell
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
Carlos A
CA
Castellanos
Department of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA. Electronic address: mike.king@cornell.edu.
Michael R
MR
King
D000538:Aluminum Silicates / Q000737:chemistry; D001672:Biocompatible Materials / Q000737:chemistry*; D015415:Biomarkers / Q000378:metabolism; D001773:Blood Cells / Q000166:cytology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002469:Cell Separation; D000077215:Clay; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008024:Ligands; D061986:MCF-7 Cells; D043942:Nanotubes / Q000737:chemistry*; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology; D011379:Prognosis; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D019087:Selectins / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
D000538:Aluminum Silicates; D001672:Biocompatible Materials; D015415:Biomarkers; D008024:Ligands; D000644:Quaternary Ammonium Compounds; D019087:Selectins; D013501:Surface-Active Agents; C013912:decyltrimethylammonium; D000077215:Clay
Biomaterials; Circulating tumor cell; Halloysite; Leukocyte; Metastasis; Surfactant