Clinically-applicable perfluorocarbon-loaded nanoparticles for in vivo photoacoustic,19f magnetic resonance and fluorescent imaging

Edyta Swider, Khalid Daoudi, Alexander H.J. Staal, Olga Koshkina, N. Koen van Riessen, Eric van Dinther, I. Jolanda M. de Vries, Chris L. de Korte, Mangala Srinivas
Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect. Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA,19F MR, and fluorescence imaging in vitro and in vivo. Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x106 cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles. Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and19F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use.

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