TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis

Research output: Contribution to journalArticle

Eszter Voros, Minjung Cho, Maricela Ramirez, Anna Lisa Palange, Enrica De Rosa, Jaehong Key, Zsolt Garami, Alan B. Lumsden, Paolo Decuzzi

The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA-NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100-fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10-fold) by mild, localized heating resulting from the exposure of tPA-NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA-NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10-3 m-1 s-1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA-NCs a promising nano-theranosis agent in thrombotic disease.

Original languageEnglish (US)
Pages (from-to)1709-1718
Number of pages10
JournalAdvanced Functional Materials
Volume25
Issue number11
DOIs
StatePublished - Jan 21 2015

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TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis. / Voros, Eszter; Cho, Minjung; Ramirez, Maricela; Palange, Anna Lisa; De Rosa, Enrica; Key, Jaehong; Garami, Zsolt; Lumsden, Alan B.; Decuzzi, Paolo.

In: Advanced Functional Materials, Vol. 25, No. 11, 21.01.2015, p. 1709-1718.

Research output: Contribution to journalArticle

Harvard

Voros, E, Cho, M, Ramirez, M, Palange, AL, De Rosa, E, Key, J, Garami, Z, Lumsden, AB & Decuzzi, P 2015, 'TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis' Advanced Functional Materials, vol. 25, no. 11, pp. 1709-1718. https://doi.org/10.1002/adfm.201404354

APA

Voros, E., Cho, M., Ramirez, M., Palange, A. L., De Rosa, E., Key, J., ... Decuzzi, P. (2015). TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis. Advanced Functional Materials, 25(11), 1709-1718. https://doi.org/10.1002/adfm.201404354

Vancouver

Voros E, Cho M, Ramirez M, Palange AL, De Rosa E, Key J et al. TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis. Advanced Functional Materials. 2015 Jan 21;25(11):1709-1718. https://doi.org/10.1002/adfm.201404354

Author

Voros, Eszter ; Cho, Minjung ; Ramirez, Maricela ; Palange, Anna Lisa ; De Rosa, Enrica ; Key, Jaehong ; Garami, Zsolt ; Lumsden, Alan B. ; Decuzzi, Paolo. / TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis. In: Advanced Functional Materials. 2015 ; Vol. 25, No. 11. pp. 1709-1718.

BibTeX

@article{8f09d9901e634e35847cf471ea21b82a,
title = "TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis",
abstract = "The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA-NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100-fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10-fold) by mild, localized heating resulting from the exposure of tPA-NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA-NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10-3 m-1 s-1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA-NCs a promising nano-theranosis agent in thrombotic disease.",
keywords = "hyperthermia, nanoparticles, theranosis, thrombosis",
author = "Eszter Voros and Minjung Cho and Maricela Ramirez and Palange, {Anna Lisa} and {De Rosa}, Enrica and Jaehong Key and Zsolt Garami and Lumsden, {Alan B.} and Paolo Decuzzi",
year = "2015",
month = "1",
day = "21",
doi = "10.1002/adfm.201404354",
language = "English (US)",
volume = "25",
pages = "1709--1718",
journal = "Advanced Functional Materials",
issn = "1616-301X",
publisher = "Wiley",
number = "11",

}

RIS

TY - JOUR

T1 - TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis

AU - Voros, Eszter

AU - Cho, Minjung

AU - Ramirez, Maricela

AU - Palange, Anna Lisa

AU - De Rosa, Enrica

AU - Key, Jaehong

AU - Garami, Zsolt

AU - Lumsden, Alan B.

AU - Decuzzi, Paolo

PY - 2015/1/21

Y1 - 2015/1/21

N2 - The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA-NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100-fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10-fold) by mild, localized heating resulting from the exposure of tPA-NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA-NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10-3 m-1 s-1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA-NCs a promising nano-theranosis agent in thrombotic disease.

AB - The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA-NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100-fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10-fold) by mild, localized heating resulting from the exposure of tPA-NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA-NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10-3 m-1 s-1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA-NCs a promising nano-theranosis agent in thrombotic disease.

KW - hyperthermia

KW - nanoparticles

KW - theranosis

KW - thrombosis

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U2 - 10.1002/adfm.201404354

DO - 10.1002/adfm.201404354

M3 - Article

VL - 25

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EP - 1718

JO - Advanced Functional Materials

T2 - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-301X

IS - 11

ER -

ID: 32338705