A t-PA/nanoparticle conjugate with fully retained enzymatic activity and prolonged circulation time

Abstract

A major issue in the therapeutic use of tissue plasminogen activator (t-PA) for the treatment of thrombotic diseases is its very short half-life in the circulation due to the effects of inhibitors. The present study aims to resolve the issue using a t-PA/gold nanoparticle (t-PA/AuNP) conjugate prepared via bio-affinity ligation under physiological conditions. The ligation is based on the specific interactions between t-PA and ε-lysine (a ligand that has affinity to a specific domain in t-PA) immobilized on the AuNP surface through polyvinyl pyrrolidone (PVP) as a spacer. The conjugate can not only retain almost full enzymatic activity and clot dissolving efficiency, but also protect t-PA from inhibition by PAI-1 to some extent as compared with free t-PA in vitro. Moreover, the conjugate showed prolonged circulation time in vivo.