Dopamine-functionalized hyaluronic acid microspheres for effective capture of CD44-overexpressing circulating tumor cells

Abstract

As one of the biomarkers of liquid biopsy, circulating tumor cells (CTCs) provides important clinical information for cancer diagnosis. However, accurate separation and identification of CTCs remains a great deal of challenge. In present work, we developed novel dopamine-functionalized hyaluronic acid microspheres (HA-DA microspheres) to capture CD44-overexpressing CTCs. The dopamine was grafted onto the hyaluronic acid chain, which was polymerized and cross-linked by oxidation of the catechol groups. Afterwards, a facile microfluidic chip was designed and developed to fabricate the HA-DA microspheres with a diameter of about 45 μm. Our results showed that the CD44+ cells (i.e., HeLa, HepG2, A549, MCF-7 and DU-145 cells) could be selectively captured. Then a double-layer microfluidic filter (DLMF) was fabricated for dynamic isolation and detection of CTCs in blood samples. Many slit openings with 15 μm in height were designed to allow white blood cells to clear away, while the microspheres with CTCs were intercepted in the DLMF, which achieved effective separation of CTCs from blood cells. The approach exhibited high capture efficiency even at the cell density as low as 10 cells/mL. We believe the DLMF integrated with HA-DA microspheres could be a promising approach for isolation and detection of CD44-overexpressing CTCs, which is useful for prognosis and early metastasis of cancer patients.