Fate and biological impact of persistent luminescence nanoparticles after injection in mice: a one-year follow-up.

Persistent luminescence nanoparticles (PLNPs) are attracting growing interest for non-invasive optical imaging of tissues with a high signal to noise ratio. PLNPs can emit a persistent luminescence signal through the tissue transparency window for several minutes, after UV light excitation before systemic administration or directly in vivo through visible irradiation, allowing us to get rid of the autofluorescence signal of tissues. PLNPs constitute a promising alternative to the commercially available optical near infrared probes thanks to their versatile functionalization capabilities for improvement of the circulation time in the blood stream. Nevertheless, while biodistribution for a short time is well known, the long-term fate and toxicity of the PLNP's inorganic core after injection have not been dealt with in depth. Here we extend the current knowledge on ZnGa1.995O4Cr0.005 NPs (or ZGO) with a one-year follow-up of their fate after a single systemic administration in mice. We investigated the organ tissue uptake of ZGO with two different coatings and determined their intracellular processing up to one year after injection. The biopersistence of ZGO was assessed, with a long-term retention, quantified by ICP-MS, mostly in the liver and spleen, parallel with a loss of their luminescence properties. The analysis of the toxicity related to combining an animal's weight, key hematological and metabolic markers, histological observations of liver tissues and quantification of the expression of 31 genes linked to different metabolic reactions did not reveal any signs of noxiousness, from the macro scale to the molecular level. Therefore, the ZGO imaging probe has been proven to be a safe and relevant candidate for preclinical studies, allowing its long term use without any in vivo disturbance of the general metabolism.

Level of Onboard Care for Critical Patients: Analysis of the French Armed Forces Air Medical Evacuations From the Sahel Since 2013.

OBJECTIVE: Since 2013, the French Armed Forces have been engaged in the Sahel. The aim of our work was to study the characteristics of severe patients evacuated according to the composition of the air medical staff (ie, an anesthesiologist/intensive care physician [AICP] or an emergency physician [EP]). METHODS: This was a retrospective cohort analysis including all French service members repatriated from the Sahel with a speedy evacuation priority between 2013 and 2019. RESULTS: A total of 191 patients were evacuated. The causes were trauma for 103 patients and disease for 88. Trauma patients included war injuries (n = 58) and nonbattle injuries (n = 44). For disease patients, the main pathologies were cardiovascular (n = 17), infectious (n = 17), neurologic (n = 15), and gastrointestinal (n = 12). Highly dependent patients were significantly (P < .001) more likely to be managed by an AICP (n = 41) than an EP (n = 5). Moderately dependent patients managed by an AICP (n = 51) were more frequently unstable hemodynamically (n = 5 vs. n = 0, P < .05) and referred to an intensive care unit (n = 24 vs. n = 2, P < .001) than those managed by an EP (n = 41). There were no deaths in flight. CONCLUSION: Greater use of EPs, especially for transporting stabilized patients, would provide more personnel trained in long-distance air transport.

Persistent luminescence nanoparticles functionalized by polymers bearing phosphonic acid anchors: synthesis, characterization, and in vivo behaviour.

Optical in vivo imaging has become a widely used technique and is still under development for clinical diagnostics and treatment applications. For further development of the field, researchers have put much effort into the development of inorganic nanoparticles (NPs) as imaging probes. In this trend, our laboratory developed ZnGa1.995O4Cr0.005 (ZGO) nanoparticles, which can emit a bright persistent luminescence signal through the tissue transparency window for dozens of minutes and can be activated in vivo with visible irradiation. These properties endow them with unique features, allowing us to recover information over a long-time study with in vivo imaging without any background. To target tissues of interest, ZGO must circulate long enough in the blood stream, a phenomenon which is limited by the mononuclear phagocyte system (MPS). Depending on their size, charge and coating, the NPs are sooner or later opsonized and stored into the main organs of the MPS (liver, spleen, and lungs). The NPs therefore have to be coated with a hydrophilic polymer to avoid this limitation. To this end, a new functionalization method using two different polyethylene glycol phosphonic acid polymers (a linear one, later named lpPEG and a branched one, later named pPEG) has been studied in this article. The coating has been optimized and characterized in various aqueous media. The behaviour of the newly functionalized NPs has been investigated in the presence of plasmatic proteins, and an in vivo biodistribution study has been performed. Among them ZGOpPEG exhibits a long circulation time, corresponding to low protein adsorption, while presenting an effective one-step process in aqueous medium with a low hydrodynamic diameter increase. This new method is much more advantageous than another strategy we reported previously that used a two-step PEG silane coating performed in an organic solvent (dimethylformamide) for which the final hydrodynamic diameter was twice the initial diameter.

Coating Persistent Luminescence Nanoparticles With Hydrophilic Polymers for in vivo Imaging.

Persistent luminescence nanoparticles (PLNPs) are innovative nanomaterials highly useful for bioimaging applications. Indeed, due to their particular optical properties, i.e., the ability to store the excitation energy before slowly releasing it for a prolonged period of time, they allow in vivo imaging without auto-fluorescence and with a high target to background ratio. However, as for most nanoparticles (NPs), without any special surface coating, they are rapidly opsonized and captured by the liver after systemic injection into small animals. To overcome this issue and prolong nanoparticle circulation in the bloodstream, a new stealth strategy was developed by covering their surface with poly(N-2-hydroxypropyl)methacrylamide (pHPMA), a highly hydrophilic polymer widely used in nanomedicine. Preliminary in vivo imaging results demonstrated the possibility of pHPMA as an alternative strategy to cover ZnGa2O4:Cr NPs to delay their capture by the liver, thereby providing a new perspective for the formulation of stealth NPs.

Degradation of ZnGa2O4:Cr3+ luminescent nanoparticles in lysosomal-like medium.

The ultimate goal of in vivo imaging is to provide safe tools to probe the inside of a body in order to obtain pathological information, monitor activities, and examine disease progression or regression. In this context zinc gallate doped with chromium III (ZGO) nanoparticles with persistent luminescence properties have been previously developed, and their biodistribution as well as in vitro toxicity were evaluated. However, to date, nothing is known about their potential transformations in biological media, which may hinder their biomedical applications. In order to know if these nanoparticles could degrade, the present work consists of studying their fate over time depending on both their coating and the aqueous media in which they are dispersed. ZGO nanoparticles have been dispersed in three different aqueous solutions for up to 90 days and characterized by numerous techniques. Among the evaluated dispersion media, Artificial Lysosomal Fluid (ALF) mimicking the intracellular lysosome environment elicited significant degradation of ZGO nanoparticles. The chelating agents present in ALF have proved to play a major role in the degradation of the ZGO, by stabilizing the nanoparticles and increasing the contact. An important time decrease of the luminescence properties has also been observed, which correlated with the release of ions from ZGO nanoparticles as well as their decreasing size. This information is valuable since it indicates, for the first time, the long-term degradation of persistent luminescent nanoprobes in an in vivo like model medium. Therefore, possible elimination of the imaging probes after in vivo preclinical applications could be foreseen.

Imaging and therapeutic applications of persistent luminescence nanomaterials.

The development of probes for biomolecular imaging and diagnostics is a very active research area. Among the different imaging modalities, optics emerged since it is a noninvasive and cheap imaging technique allowing real time imaging. In vitro, this technique is very useful however in vivo, fluorescence suffers from low signal-to-noise ratio due to tissue autofluorescence under constant excitation. To address this limitation, novel types of optical nanoprobes are actually being developed and among them, persistent luminescence nanoparticles (PLNPs), with long lasting near-infrared (NIR) luminescence capability, allows doing optical imaging without constant excitation and so without autofluorescence. This review will begin by introducing the physical phenomenon associated to the long luminescence decay of such nanoprobes, from minutes to hours after ceasing the excitation. Then we will show how this property can be used to develop in vivo imaging probes and also more recently nanotheranostic agents. Finally, preliminary data on their biocompatibility will be mentioned and we will conclude by envisioning on the future applications and improvements of such nanomaterials.

Chemically engineered persistent luminescence nanoprobes for bioimaging.

Imaging nanoprobes are a group of nanosized agents developed for providing improved contrast for bioimaging. Among various imaging probes, optical sensors capable of following biological events or progresses at the cellular and molecular levels are actually actively developed for early detection, accurate diagnosis, and monitoring of the treatment of diseases. The optical activities of nanoprobes can be tuned on demand by chemists by engineering their composition, size and surface nature. This review will focus on researches devoted to the conception of nanoprobes with particular optical properties, called persistent luminescence, and their use as new powerful bioimaging agents in preclinical assays.