Research Article

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2016, 9(5): 1276–1289

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https://doi.org/10.1007/s12274-016-1023-z

Targeted nanoparticles for the non-invasive detectionof traumatic brain injury by optical imaging and fluorinemagnetic resonance imaging

Luis Javier Cruz1 (*), Ivo Que1, Markus Aswendt2, Alan Chan1,3, Mathias Hoehn1,2, and Clemens Lwik1 (*)

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1 Nanomedicine and Molecular Imaging, Department of Radiology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands
2 In-Vivo-NMR Laboratory, Max Planck Institute for Neurological Research Cologne, D-50931 Cologne, Germany
3 Percuros, 7522NB Enschede, The Netherlands

Keywords: imaging,nanoparticles,contrast agents,magnetic resonanceimaging,brain injury,stroke
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  • Abstract
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Necrosis is a form of cell death that occurs only under pathological conditionssuch as ischemic diseases and traumatic brain injury (TBI). Non-invasive imagingof the affected tissue is a key component of novel therapeutic interventions andmeasurement of treatment responses in patients. Here, we report a bimodalapproach for the detection and monitoring of TBI. PEGylated poly(lactic-coglycolicacid) (PLGA) nanoparticles (NPs), encapsulating both near infrared (NIR)fluorophores and perfluorocarbons (PFCs), were targeted to necrotic cells. Weused cyanine dyes such as IRDye 800CW, for which we have previouslydemonstrated specific targeting to intracellular proteins of cells that have lostmembrane integrity. Here, we show specific in vivo detection of necrosis by opticalimaging and fluorine magnetic resonance imaging (19F MRI) using newly designedPLGA NP(NIR700 + PFC)-PEG-800CW. Quantitative ex vivo optical imaging and19F MR spectroscopy of NIR-PFC content in injured brain regions and in majororgans were well correlated. Both modalities allowed the in vivo identificationof necrotic brain lesions in a mouse model of TBI, with optical imaging beingmore sensitive than 19F MRI. Our results confirm increased blood pool residencetime of PLGA NPs coated with a PEG layer and the successful targeting ofTBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapidqualitative optical monitoring of the TBI state and quantitative 3D informationfrom deeper tissues on the extent of the lesion by MRI. These necrosis-targetingPLGA NPs can potentially be used for clinical diagnosis of brain injuries.
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Targeted nanoparticles for the non-invasive detectionof traumatic brain injury by optical imaging and fluorinemagnetic resonance imaging. Nano Res. 2016, 9(5): 1276–1289 https://doi.org/10.1007/s12274-016-1023-z

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