Cell surface functionalization with lysine ligand-containing copolymers for fibrinolytic activity

Abstract

Although cell transplantation has achieved great success in the treatment of many intractable diseases, due to the effect of an instant blood-mediated inflammatory reaction (IBMIR), blood clots usually form on the surface of transplanted cells, resulting in a significant reduction in the survival of transplanted cells. Inspired by the fibrinolytic mechanism in human blood, this paper constructs lysine ligand-containing copolymer-functionalized cell surfaces for fibrinolytic activity. First, a copolymer (POLF) of oligoethylene glycol methacrylate (OEGMA), 6-amino-2-(2-methacylamido)-hexanoic acid (Lys) and fluorescein O-methacrylate (FluMA) was synthesized by reversible addition–fragmentation chain transfer (RAFT) copolymerization. Then, the copolymer POLF was modified onto the HeLa cell surface by codeposition with dopamine. An in vitro study showed that compared to unmodified HeLa cells, modified cells not only have good cell viability but can also resist fibrinogen adsorption and selectively bind plasminogen from plasma. More importantly, upon activation of plasminogen adsorbed to plasmin, the modified cells were able to rapidly lyse fibrin formed on their surface. This study offers a novel proof-of-concept for constructing transplanted cells with fibrinolytic activity.