Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles

S. Sibel Erdem, Irina Y. Sazonova, Tetsuya Hara, Farouc A. Jaffer, Jason R. McCarthy

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Scopus citations

Abstract

Thrombosis, the formation of a clot within a blood vessel, underlies a number of life-threatening cardiovascular disorders such as heart attack, ischemic stroke, pulmonary embolism, and deep vein thrombosis. These conditions affect the lives of millions of people worldwide and result in significant morbidity and mortality. It is thus crucial to develop novel methodologies to enhance the detection and treatment of these disorders. Thrombolysis, or the dissolution of blood clots, relies upon the administration of exogenous plasminogen activators (PAs) that lyse fibrin. Yet, there are several drawbacks to the use of current PAs, including significant risks of uncontrolled bleeding and suboptimal efficacy and pharmacokinetics. Nanomaterials are well positioned to address these priority issues in thrombolysis, via the alteration of PA pharmacokinetics and biodistribution. Additionally, due to the multifunctional nature of nanoparticles, these thrombolytics may be targeted to the site of occlusion, effectively concentrating the drug where it is most needed. Herein, we describe the methodology associated with the synthesis of a novel thrombus-targeted fibrinolytic nanoagent. At each step of the synthesis, we analyze the nanomaterials, including their physical properties and their ability to bind to thrombosis targets of interest. The effect of the conjugation of tPA to the nanoparticle surface on the amidolytic and fibrinolytic activities of nanoagents is also investigated. Lastly, the in vivo binding of the targeted thrombolytic to intravascular thrombi is examined.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
PublisherAcademic Press Inc.
Pages191-209
Number of pages19
DOIs
StatePublished - 2012

Publication series

NameMethods in Enzymology
Volume508
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Iron oxide
  • Nanomedicine
  • Peptide-targeted
  • Plasminogen activator
  • Thrombolysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles'. Together they form a unique fingerprint.

  • Cite this

    Erdem, S. S., Sazonova, I. Y., Hara, T., Jaffer, F. A., & McCarthy, J. R. (2012). Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles. In Methods in Enzymology (pp. 191-209). (Methods in Enzymology; Vol. 508). Academic Press Inc.. https://doi.org/10.1016/B978-0-12-391860-4.00010-0