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Issue 6, 2015
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A t-PA/nanoparticle conjugate with fully retained enzymatic activity and prolonged circulation time

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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.

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

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Publication details

The article was received on 30 Sep 2014, accepted on 21 Dec 2014 and first published on 23 Dec 2014


Article type: Paper
DOI: 10.1039/C4TB01625D
Citation: J. Mater. Chem. B, 2015,3, 977-982
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    A t-PA/nanoparticle conjugate with fully retained enzymatic activity and prolonged circulation time

    Z. Tang, D. Li, X. Wang, H. Gong, Y. Luan, Z. Liu, J. L. Brash and H. Chen, J. Mater. Chem. B, 2015, 3, 977
    DOI: 10.1039/C4TB01625D

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