Differentially charged nanomaterials control selectin-mediated adhesion and isolation of cancer cells and leukocytes 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. Biomimetic flow devices 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, we developed surfaces of nanoscale roughness and varying surface charge for E-selectin mediated adhesion and separation of cancer cells and leukocytes from flow. Halloysite nanotubes (HNTs) functionalized with the negatively charged surfactant sodium dodecanoate (NaL) significantly increased the number of colon and breast cancer cells captured from flow. Conversely, HNT functionalization with the positively charged surfactant decyl trimethyl ammonium bromide (DTAB) abrogated nearly all cancer cell adhesion to E-selectin (ES). The opposite trend was observed with leukocytes, with decreased cell adhesion to E-selectin on NaL-functionalized HNTs, and increased adhesion to DTAB-functionalized HNTs. This work reveals that differentially charged nanomaterials can control receptor-mediated cancer cell and leukocyte adhesion, enabling new approaches to increase the number and purity of separated CTCs from patient blood.