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Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury (TBI). Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), encapsulating both near infrared (NIR) fluorophores and perfluorocarbons (PFCs), were targeted to necrotic cells. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging (19F MRI) using newly designed PLGA NP(NIR700 + PFC)-PEG-800CW. Quantitative ex vivo optical imaging and 19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than 19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.

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Publication history

Received: 15 September 2015
Revised: 12 January 2016
Accepted: 16 January 2016
Published: 29 September 2016
Issue date: May 2016

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© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Acknowledgements

Acknowledgments

The authors wish to thank the technicians of the LUMC Radiology Department and Andreas Beyrau (MPI for Neurological Research in Cologne) for assistance. This work was financially supported by the EU-FP7 programs TargetBraIn (No. HEALTH-F2-2012-279017), BrainPath (No. PIAPP-GA-2013-612360), and CTMM project Cancer Vaccine Tracking (No. 03O-302).

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Email: nanores@tup.tsinghua.edu.cn

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