Theranastic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation

Twan Gerardus Gertudis Maria Lammers, Patrick Koczera, Stanley Fokong, Felix Gremse, Josef Ehling, Michael Vogt, Andrij Pich, Gerrit Storm, Marc van Zandvoort, Fabian Kiessling

Research output: Contribution to journalArticleAcademicpeer-review

64 Citations (Scopus)

Abstract

Efficient and safe drug delivery across the blood-brain barrier (BBB) remains one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO-MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non-invasive R 2*-based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R 2* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)-dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders.
Original languageUndefined
Pages (from-to)36-43
JournalAdvanced functional materials
Volume25
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • METIS-315201
  • IR-99928

Cite this

Lammers, Twan Gerardus Gertudis Maria ; Koczera, Patrick ; Fokong, Stanley ; Gremse, Felix ; Ehling, Josef ; Vogt, Michael ; Pich, Andrij ; Storm, Gerrit ; van Zandvoort, Marc ; Kiessling, Fabian. / Theranastic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation. In: Advanced functional materials. 2015 ; Vol. 25, No. 1. pp. 36-43.
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abstract = "Efficient and safe drug delivery across the blood-brain barrier (BBB) remains one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO-MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non-invasive R 2*-based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R 2* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)-dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders.",
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author = "Lammers, {Twan Gerardus Gertudis Maria} and Patrick Koczera and Stanley Fokong and Felix Gremse and Josef Ehling and Michael Vogt and Andrij Pich and Gerrit Storm and {van Zandvoort}, Marc and Fabian Kiessling",
year = "2015",
doi = "10.1002/adfm.201401199",
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Lammers, TGGM, Koczera, P, Fokong, S, Gremse, F, Ehling, J, Vogt, M, Pich, A, Storm, G, van Zandvoort, M & Kiessling, F 2015, 'Theranastic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation' Advanced functional materials, vol. 25, no. 1, pp. 36-43. https://doi.org/10.1002/adfm.201401199

Theranastic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation. / Lammers, Twan Gerardus Gertudis Maria; Koczera, Patrick; Fokong, Stanley; Gremse, Felix; Ehling, Josef; Vogt, Michael; Pich, Andrij; Storm, Gerrit; van Zandvoort, Marc; Kiessling, Fabian.

In: Advanced functional materials, Vol. 25, No. 1, 2015, p. 36-43.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Theranastic USPIO-loaded microbubbles for mediating and monitoring blood-brain barrier permeation

AU - Lammers, Twan Gerardus Gertudis Maria

AU - Koczera, Patrick

AU - Fokong, Stanley

AU - Gremse, Felix

AU - Ehling, Josef

AU - Vogt, Michael

AU - Pich, Andrij

AU - Storm, Gerrit

AU - van Zandvoort, Marc

AU - Kiessling, Fabian

PY - 2015

Y1 - 2015

N2 - Efficient and safe drug delivery across the blood-brain barrier (BBB) remains one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO-MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non-invasive R 2*-based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R 2* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)-dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders.

AB - Efficient and safe drug delivery across the blood-brain barrier (BBB) remains one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, it is demonstrated that poly(butyl cyanoacrylate)-based microbubbles (MB), carrying ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles within their shell, can be used to mediate and monitor BBB permeation. Upon exposure to transcranial ultrasound pulses, USPIO-MB are destroyed, resulting in acoustic forces inducing vessel permeability. At the same time, USPIO are released from the MB shell, they extravasate across the permeabilized BBB and they accumulate in extravascular brain tissue, thereby providing non-invasive R 2*-based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R 2* relaxometry are in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug fluorescein isothiocyanate (FITC)-dextran into the brain. Such theranostic materials and methods are considered to be useful for mediating and monitoring drug delivery across the BBB and for enabling safe and efficient treatment of CNS disorders.

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KW - IR-99928

U2 - 10.1002/adfm.201401199

DO - 10.1002/adfm.201401199

M3 - Article

VL - 25

SP - 36

EP - 43

JO - Advanced functional materials

JF - Advanced functional materials

SN - 1616-301X

IS - 1

ER -