Theranostic USPIO-Loaded Microbubbles for Mediating and Monitoring Blood-Brain Barrier Permeation.
Efficient and safe drug delivery across the blood-brain barrier (BBB) remains to be one of the major challenges of biomedical and (nano-) pharmaceutical research. Here, we show 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 R2*-based magnetic resonance imaging information on the extent of BBB opening. Quantitative changes in R2* relaxometry were in good agreement with 2D and 3D microscopy results on the extravascular deposition of the macromolecular model drug 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.
Department for Experimental Molecular Imaging University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Pauwelsstrasse 20, 52074 Aachen (Germany) Tel: +49-241-8080116; ; Department of Controlled Drug Delivery MIRA Institute for Biomedical Engineering and Technical Medicine University of Twente, Enschede (The Netherlands); Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht (The Netherlands).
Twan
T
Lammers
Department for Experimental Molecular Imaging University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Pauwelsstrasse 20, 52074 Aachen (Germany) Tel: +49-241-8080116.
Patrick
P
Koczera
Department for Experimental Molecular Imaging University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Pauwelsstrasse 20, 52074 Aachen (Germany) Tel: +49-241-8080116.
Stanley
S
Fokong
Department for Experimental Molecular Imaging University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Pauwelsstrasse 20, 52074 Aachen (Germany) Tel: +49-241-8080116.
Felix
F
Gremse
Department for Experimental Molecular Imaging University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Pauwelsstrasse 20, 52074 Aachen (Germany) Tel: +49-241-8080116.
Josef
J
Ehling
Institute for Molecular Cardiovascular Research (IMCAR) University Clinic, RWTH Aachen University, Aachen (Germany).
Michael
M
Vogt
Functional and Interactive Polymers, DWI, Leibniz Centre for Interactive Materials RWTH Aachen University, Aachen (Germany).
Andrij
A
Pich
Department of Controlled Drug Delivery MIRA Institute for Biomedical Engineering and Technical Medicine University of Twente, Enschede (The Netherlands); Department of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University, Utrecht (The Netherlands).
Gert
G
Storm
Institute for Molecular Cardiovascular Research (IMCAR) University Clinic, RWTH Aachen University, Aachen (Germany); Department of Genetics and Cell Biology Cardiovascular Research Institute Maastricht (CARIM) Maastricht University, Maastricht (The Netherlands).
Marc
M
van Zandvoort
Department for Experimental Molecular Imaging University Clinic and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Pauwelsstrasse 20, 52074 Aachen (Germany) Tel: +49-241-8080116.
Fabian
F
Kiessling
Drug Delivery; Hybrid Materials; Magnetic Nanoparticles; Medical Applications; Stimuli-Responsive Materials