Long-term prevalence of NIRF-labeled magnetic nanoparticles for the diagnostic and intraoperative imaging of inflammation

Abstract

Inflammation is a very common disease worldwide. In severe cases, surgery is often the method of choice. Today, there is a general need for the implementation of image-based guidance methodologies for reliable target resection. We investigated new near infrared fluorescence (NIRF)-nanoparticles (NPs) as a simple but effective bimodal magnetic resonance imaging (MRI) and optical contrast agent for diagnosis and intraoperative imaging of inflammation. Physicochemical analysis revealed that these NPs were highly fluorescent with similar characteristics like unlabeled NPs (hydrodynamic diameter about 130 nm and zeta potential about −10 mV). NP-uptake and NIR-dye labeling was biocompatible to macrophages (no impact on cellular ATP and reactive oxygen species production). These cells could successfully be tracked with MRI and NIRF-optical imaging. I.v. injection of fluorescent NPs into mice led to highly specific T₂-weighted signal of edema due to uptake by phagocytic cells and subsequent migration to the site of inflammation. NIRF signals of the edema region were well detectable for up to 4 weeks, underlining the potential of the NPs for systematic planning and flexible time scheduling in intraoperative applications. NPs were degraded over a time period of 12 weeks, which was not altered due to inflammation. Redistribution of iron might be primarily due to inflammation and not to the presence of NPs per se in a concentration suitable for imaging. Our findings highlight the potential of the NPs to be used as a suitable tool for pre- and intraoperative imaging of inflammation.

• Biocompatibility
• biodistribution
• degradation
• MRI
• optical imaging

Acknowledgements

We gratefully acknowledge Andreas Kalytta-Mewes and Prof. Dr Dirk Volkmer (University of Augsburg, Institute of Physics, Chair of Solid State Chemistry) for performing BET-measurement. We thank Katja Haedicke and Doreen May for technical assistance during the mice edema studies and Julia Göring for the treatment and histological staining of mice organs. We would also like to thank Martin Böttcher (University Hospital Jena, Institute for Immunology) for valuable tips concerning ELISA studies and in vivo investigations. Furthermore, we are grateful to Prof. Dr Biskup (University Hospital Jena, Group Biomolecular Biophotonics) and Florian Schlenk (University Jena, Faculty of Biology and Pharmacy) for supporting the performance on photon correlation spectroscopy and zeta potential measurements.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper. Support of the Bundesministerium für Bildung und Forschung (BMBF) is gratefully acknowledged (project NanoMed).

Supplementary material available online

Supplementary Figures 1-3.