Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles.

摘要: We investigated the feasibility and efficacy of target thrombolysis with recombinant tissue plasminogen activator (rtPA) covalently bound to magnetic nanoparticle (MNP) retained site in vivo by an external magnet. Polyacrylic acid-coated magnetite (PAA-MNP, 246 nm) was synthesized characterized; rtPA immobilized PAA-MNP through carbodiimide-mediated amide bond formation. The enzyme activities rtPA, as measured a chromogenic substrate assay (125)I-fibrinolysis assay, were 87+/-1% 86+/-3% that free rtPA. Under guidance magnet moving back forth along iliac artery, thrombolytic activity PAA-MNP-rtPA equivalent 0.2mg/kg determined flowmetry rat embolic model. Intra-arterial administration restored blood flow within 75 min 82% before clot lodging, whereas amount or exerted no improvement on hemodynamics. At end 2-h period, did not alter levels hemoglobin, hematocrit, cell count. In conclusion, immobilization covalent binding resulted stable preparation predictable around under guidance; this approach may achieve reproducible effective <20% regular dose