Clinically-Applicable Perfluorocarbon-Loaded Nanoparticles For In vivo Photoacoustic, ¹⁹F Magnetic Resonance And Fluorescent Imaging

Abstract

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 and 19F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use.

State-of-the-Art Preclinical Photoacoustic Imaging in Oncology: Recent Advances in Cancer Theranostics

“…After intravenous (IV) injection, ICG rapidly binds albumin, establishing macromolecules that are unable to permeate the endothelium of many organs. In clinical field, ICG has been used for angiography, liver functional evaluation, and SLNs detection by FL and PA imaging, while in preclinical research, it has been proposed for monitoring tumor growth and therapeutic efficacy [24, 25]. PAI using ICG has been proven to provide early detection of neoangiogenesis in growing neoplasia such as a Lewis lung carcinoma mouse model, based on EPR effect exerted by ICG-albumin macromolecules within the tumor environment [26].…”

“…In vitro studies showed that the apoptotic effect of ICG after NIR irradiation is essentially mediated by heat and ROS generation, as confirmed in vivo by detection of tumor growth suppression in the Huh7 xenograft mouse model. Although ICG has been used to enhance the PA signal in tumor lesions, this simple contrast agent shows limited applications due to its lacks of specificity, rapid clearance, low photo stability, low water solubility, and tendency to form aggregates [24, 25]. Circulation time and photostability of ICG-based contrast agents have been improved through the encapsulation within NPs, for example, entrapping a high number of dye molecules into bigger NPs using the PEBBLE (photonic explorers for biomedical use by biologically localized embedding) technology.…”

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

“…The encapsulation of ICG within NPs decreases its photobleaching and increases the retention of signals within the cells. It can detect as little as 0.1 × 10 6 cells in PAI and the nanocomplex [ 123 ]. Core–shell silica PEG NPs were developed with photothermal, photoacoustic, and NIR optical imaging properties.…”

<p>Perfluorocarbons-Based ¹⁹F Magnetic Resonance Imaging in Biomedicine</p>

“…154 This work showed the potential of labeled primary human dendritic cells for cell imaging and lymph node detection with PAI and 19 F MRI. 155 Thus, 19 F MRI is an effective method of monitoring immune cell therapy.…”