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7 5 I H I G H L I G H T S 2 0 2 1
PRINCIPAL PUBLICATION AND AUTHORS
Multimodal imaging with NanoGd reveals spatiotemporal features of neuroinflammation after experimental stroke, V. Hubert (a), I. Hristovska (b), S. Karpati (c), S. Benkeder (b), A. Dey (d), C. Dumot (a), C. Amaz (e), N. Chounlamountri (b), C. Watrin (b), J.C. Comte (f), F. Chauveau (f), E. Brun (g), P. Marche (d), F. Lerouge (c), S. Parola (c), Y. Berthezène (h), T. Vorup-Jensen (i), O. Pascual (b), M. Wiart (a), Adv. Sci. e2101433 (2021); https:/doi.org/10.1002/advs.202101433 (a) Univ. Lyon, Inserm U1060, CarMeN, Lyon (France) (b) Univ. Lyon, Inserm U1217, CNRS UMR 5310, INMG, Lyon (France) (c) Univ. Lyon, ENS Lyon, CNRS UMR 5182, LCH, Lyon (France) (d) UGA, CNRS UMR 5309, Inserm U1209, IAB, Grenoble (France) (e) CIC, Lyon (France) (f) Univ. Lyon, CNRS UMR 5292, Inserm U1028, CRNL, Lyon (France) (g) Inserm UA7, STROBE, Grenoble (France) (h) Univ. Lyon, CNRS UMR 5220, Inserm U1294, Creatis, Lyon (France) (i) Department of Biomedicine, University of Aarhus, Aarhus (Denmark)
REFERENCES
[1] Z.A. Fayad & C. Calcagno, JACC Cardiovasc. Imaging 14(2), 377-378 (2021). [2] S. Karpati et al., Nanoscale 13(6), 3767- 3781 (2021).
These challenges have been addressed by gathering academic and industrial experts in the fields of chemistry, biochemistry, nanotechnology, immunology and neuroimaging (ANR, www.nanobrain.fr). Collaborative papers provide a comprehensive study of the ability of a novel hybrid nanoparticle, NanoGd, to serve as a contrast agent for imaging neuro-inflammation in vivo with multiscale resolution from macroscopic to molecular level. NanoGd is composed of a core of gadolinium fluoride decorated and customised to be efficiently phagocytosed by macrophages [2]. Thanks to its magnetic and radio-opaque core, NanoGd was detected with MRI and X-ray based approaches. It was further equipped with a dedicated fluorophore to be imaged by two-photon microscopy.
NanoGd was injected intravenously to CX3CR1eGFP/+ transgenic mice expressing green fluorescence in macrophages one day after ischemic stroke, without any adverse effect, thus confirming previous safety findings. Intravital two-photon microscopy showed that the vast majority of phagocytic cells present in the lesion had
engulfed NanoGd, a proportion that reached more than 80% in the ischemic core. This region also exhibited the strongest signal voids on MRI performed in the same subjects (Figure 59a-b). Postmortem analyses confirmed the presence of NanoGd in the ischemic lesion (Figure 59c-e). Synchrotron X-ray phase-contrast tomography (XPCT) at beamline ID17 provided a 3-dimensional NanoGd-induced hyperintense signal in good spatial agreement with MRI signal voids (Figure 59c). In addition, both fluorescence microscopy and transmission electron microscopy (TEM) confirmed that NanoGd was found inside phagocytic cells in the lesion core (Figure 59d-e).
In summary, by combining state-of-the-art complementary approaches, it has been established that NanoGd-enhanced MRI may be used as a safe and reliable imaging biomarker of neuro-inflammation in the first days following ischemic stroke (Figure 59f).
Extended nucleation and superfocusing new aspects of colloidal quantum dot synthesis probed by in-situ X-ray scattering
The formation of colloidal quantum dots (QDs) was monitored in situ while mimicking actual lab- scale synthesis conditions using small-angle X-ray scattering. The time development of QD size, size dispersion and concentration sheds new light on synthesis mechanisms, which are governed by the counteracting effects of long nucleation times and strong size focusing.
Colloidal QDs have emerged as a printable light emitter or absorber for lighting, display and sensing technologies. A central asset of QDs is their emitting saturated colours that can be precisely controlled through the QD size (Figure 60a). This fine adjustment of optical properties is achieved through colloidal synthesis methods, which have been optimised through many years of research to yield QD batches with a size dispersion below 5%. Even so, the mechanism that underlies the formation of such monodisperse nanocolloids has remained unclear.
The most-often invoked mechanistic QD synthesis paradigm holds that narrow size dispersions result from
