A cell targeting and sorting approach based on the magnetophoretic capturing for early prognostics of metastatic cervical cancer cells

Abstract

HeLa cervical cancer cells are immortal with telomerase activity and metastatic characteristics similar to circulating tumor cells (CTCs). Here, we report aptamer-modified multilayered magnetic beads (Apt@MBs) that efficiently targeted and captured HeLa cells up to a low concentration of freshly prepared cell suspension (500 cells/mL). Apt@MBs were functionalized with fluorophore-conjugated AS1411-aptamer on an outer layer made up of molybdenum disulfide (MoS₂) to target nucleolin on the cell surface of captured HeLa cells. Moreover, this outer MoS₂ layer of MBs was nanoporous and could load anticancer drugs inside its porous cavities with the possibility of killing the captured and metastatic CTCs in vivo. An internal core layer of Apt@MBs consisting of Ag–Fe₃O₄ magnetic particles (MPs) was designed for magnetic manifestations and cell sorting with the possibility of screening CTCs (in the patient's blood samples) for early diagnosis of metastatic cancers. The Apt@MBs after cell capture gave rise to the heavier HeLa-MBs composites to get settled down under gravitational/inertial forces to the bottom of the tube quicker than the free cells (within 10 min). The gravitational settling of HeLa-MBs was further coupled with exposing a magnetic field to effectively capture and enrich the cells at the bottom of the tube (from 91 to 98 % cells). While the fluid containing dead, non-cancerous, or uncaptured cells in the supernatant layers were easily removed by pipetting. The HeLa-MBs after sorting out were resuspended into a fresh culture medium for further incubation or cellular analysis. Moreover, both cisplatin (CP) and epirubicin (EP) loaded Apt@MBs showed the killing of about 50 % of the captured cells. Therefore, we are confident that Apt@MBs can contribute to enumerating patients' blood samples for screening CTCs to timely and efficiently detect metastatic cancers along with the ability to effectively perform prognosis, and treatment of metastatic cancers.