Magnetic nano capture agent (MNCA)-based magnetic separation is considered as a promising approach to rapidly isolate heavy metals from blood. Limited removal efficiency and potential biosafety risks are the major challenges for the clinical use of MNCA-based magnetic separation. Here, we report a highly-efficient MNCA-based magnetic separation of heavy metals from blood in continuous multi-stage adsorption mode. The interactions between MNCA and blood components (e.g. blood cells and plasma proteins) and the MNCA-induced cellular immune responses are studied in detail. The distribution and redistribution of heavy metals in blood are quantitatively analyzed. It demonstrates that concentration dependent redistribution can increase the contact between heavy metals and MNCA, leading to improvement on heavy metal removal efficiency. The removal performance is tested in batch mode and in continuous mode. Results show that 97.97% of Pb and 96.53% of Cd are removed from blood in 120 min using continuous multi-stage adsorption mode, and the residual concentrations of Pb and Cd in blood decrease from 400 mu g L-1 to 8.11 mu g L-1 and 13.84 mu g L-1, respectively. This study paves an effective way for heavy metal intoxication therapy by MNCA-based magnetic separation. (C) 2018 Elsevier Inc. All rights reserved.