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 language | English (US) |
|---|---|
| Title of host publication | Methods in Enzymology |
| Publisher | Academic Press Inc. |
| Pages | 191-209 |
| Number of pages | 19 |
| DOIs | |
| State | Published - Jan 1 2012 |
Publication series
| Name | Methods in Enzymology |
|---|---|
| Volume | 508 |
| ISSN (Print) | 0076-6879 |
| ISSN (Electronic) | 1557-7988 |
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Keywords
- Iron oxide
- Nanomedicine
- Peptide-targeted
- Plasminogen activator
- Thrombolysis
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
Cite this
Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles. / Erdem, S. Sibel; Sazonova, Irina Yurievna; Hara, Tetsuya; Jaffer, Farouc A.; McCarthy, Jason R.
Methods in Enzymology. Academic Press Inc., 2012. p. 191-209 (Methods in Enzymology; Vol. 508).Research output: Chapter in Book/Report/Conference proceeding › Chapter
}
TY - CHAP
T1 - Detection and treatment of intravascular thrombi with magnetofluorescent nanoparticles
AU - Erdem, S. Sibel
AU - Sazonova, Irina Yurievna
AU - Hara, Tetsuya
AU - Jaffer, Farouc A.
AU - McCarthy, Jason R.
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
KW - Iron oxide
KW - Nanomedicine
KW - Peptide-targeted
KW - Plasminogen activator
KW - Thrombolysis
UR - http://www.scopus.com/inward/record.url?scp=84859063275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859063275&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-391860-4.00010-0
DO - 10.1016/B978-0-12-391860-4.00010-0
M3 - Chapter
T3 - Methods in Enzymology
SP - 191
EP - 209
BT - Methods in Enzymology
PB - Academic Press Inc.
ER -