Tailoring the Colloidal Stability, Magnetic Separability, and Cytocompatibility of High-Capacity Magnetic Anion Exchangers

Extracorporeal blood purification has been applied to artificially support kidney or liver function. However, convection and diffusion based blood purification systems have limited removal rates for high molecular weight and hydrophobic molecules. This limitation is due to the finite volume of infusion and limited membrane permeability, respectively. Adsorption provides an attractive alternative for the removal of higher molecular weight compounds. The use of adsorption resins containing ion exchanging groups to capture specific molecules has become well-established. Instead of stationary adsorption resins, however, ion exchanging polymers may be immobilized on magnetic particles and serve as freely diffusing, mobile, high capacity solid phase of ion exchange chromatography. While small beads with high surface area are attractive in terms of mass transfer and binding, unifying high capturing capacity with rapid and quantitative bead recovery remains an issue. Therefore, most of the current magnetic ion exchangers are based on micron-sized beads or require long times to separate. In addition to unfavorable magnetic recovery rates, the usually poor cytocompatibility limits their applicability in biomedicine. Here, we report on the synthesis and performance of polycationic polymer coated magnetic nanoflowers (MNF) for highly efficacious anion capturing. We demonstrate accurate control over the polymer content and composition on the beads and show its direct influence on colloidal stability, capturing capacity and magnetic separability. We present the removal of clinically relevant targets by capturing bilirubin with capacities 2-fold higher than previous work as well as quantitative heparin removal. Additionally, we illustrate how copolymerization of poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) with poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) leads to improved cytocompatibility of the polymer-coated MNF capturing agents while retaining high capturing capacities. Taken together, we present a nanoparticle/polymer material, which upon future in vivo validation, unifies high binding capacities and magnetic separability for rapid toxin capturing and hence fulfills key requirements of clinical utility.