A fibrin-specific thrombolytic nanomedicine approach to acute ischemic stroke

Jon N. Marsh, Grace Hu, Michael J. Scott, Huiying Zhang, Matthew J. Goette, Patrick J. Gaffney, Shelton D. Caruthers, Samuel A. Wickline, Dana Abendschein, Gregory M. Lanza

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Aim: To develop a fibrin-specific urokinase nanomedicine thrombolytic agent. Materials & Methods:In vitro fibrin-clot dissolution studies were utilized to develop and characterize simultaneous coupling and loading of anti-fibrin monoclonal antibody and urokinase onto perfluorocarbon nanoparticle (NP) surface. In vivo pharmacokinetics and fibrin-specific targeting of the nanolytic agent was studied in dogs. Results: Simultaneous coupling of up to 40 anti-fibrin antibodies and 400 urokinase enzymes per perfluorocarbon NP produced an effective targeted nanolytic agent with no significant surface protein-protein interference. Fibrin clot dissolution was not improved by increasing homing capacity from 10 to 40 antibodies/NP, but increasing enzymatic payload from 100 to 400/NP resulted in maximized lytic effect. Fluorescent microscopy showed that rhodamine-labeled urokinase nanoparticles densely decorated the intraluminal thrombus in canine clots in vivo analogous to the fibrin pattern, while an irrelevant-targeted agent had negligible binding. Conclusion: This agent offers a vascularly constrained, simple to administer, low-dose nanomedicine approach that may present an attractive alternative for treating acute stroke victims.

Original languageEnglish
Pages (from-to)605-615
Number of pages11
JournalNanomedicine
Volume6
Issue number4
DOIs
StatePublished - Jun 2011

Keywords

  • emergency treatment of stroke
  • nanoparticle
  • perfluorocarbon
  • targeted thrombolysis
  • urokinase

Fingerprint

Dive into the research topics of 'A fibrin-specific thrombolytic nanomedicine approach to acute ischemic stroke'. Together they form a unique fingerprint.

Cite this