We report the fine-tuning of the relaxometry of gamma-Fe2O3@SiO2 core-shell nanoparticles by adjusting the thickness of the coated silica layer. It is clear that the coating thickness of Fe2O3@SiO2 nanoparticles has a significant impact on the r(1) (at low B0 fields), r(2), and r(2)* relaxivities of their aqueous suspensions. These studies clearly indicate that the silica layer is heterogeneous and has regions that are porous to water and others-that are not. It is also shown, that the viability and the mitochondrial dehydrogenase expression of the microglial cells do not appear to be sensitive to the vesicular load with these core-shell nanoparticles. The adequate silica-shell thickness can therefore be tuned to allow for both a sufficiently high response as contrast agent, and-adequate grafting of targeted biomolecules.

Iron oxide nanoparticles with a constant superparamagnetic core coated with a silica shell with a thickness ranging from 0.6 to 71 nm were prepared by a fast and facile soft chemistry approach. The increase of the coating thickness of the γ-Fe 2 O 3 @SiO 2 nanoparticles causes a significant decrease of the r 1 and r 2 relaxivities of their aqueous suspensions. The sizes of the nanoparticles obtained by relaxometry are significantly lower than those measured by electron microscopy. Their magnetizations measured by relaxometry also decrease relative to the values obtained by magnetometry, which correspond to the core. However, this "magnetic dilution" is smaller than expected if the entire silica shell was water impermeable. Both results indicate that a significant part of the silica coating is permeable to water. The adequate silica shell thickness may, thus, be tuned to allow for both a sufficiently high response as contrast agent and an adequate grafting of targeted biomolecules.

Up-conversion (Gd,Yb,Tb)PO(4) materials and their potential for bimodal imaging have received little attention in the literature. Herein, we report the first study on the up-conversion emission of (Gd,Yb,Tb)PO(4) nanocrystals synthesized via a hydrothermal method at 150 °C. These materials exhibit ultraviolet, blue and green up-conversion emissions upon excitation with a 980 nm continuous wave laser diode. The intensity of the blue-emission band at 479 nm, ascribed to the cooperative up-conversion emission of a pair of excited Yb(3+) ions, depends on the Yb(3+)/Tb(3+) concentration ratio, calcination temperature and particle size. Strong green up-conversion emission of Tb(3+) is observed at 543 nm for the (5)D(4)→(7)F(5) transition. Relaxometry measurements reveal that the nanocrystals are efficient T(2)-weighted (negative) contrast agents which, combined with visible-light emission generated by infrared excitation, affords them considerable potential for being used in bimodal, photoluminescence-magnetic resonance, imaging.

Bimodal magnetic resonance imaging (MRI)/optical probes for bioimaging were obtained by grafting two types of lanthanide metal ions, Gd3+ and Eu3+/Tb3+, on the surface of SiO2 nanoparticles. The resulting systems were endowed with relaxometry and photoluminescent properties, respectively. Grafting a pyridine‐based aromatic backbone on to the silica surface enhances the emission quantum yield of the Eu3+‐containing nanoparticles fivefold compared to similar systems that bear no aromatic antennae. The emission properties of the mixed Ln3+/Gd3+‐based nanoparticles are not influenced by the presence of Gd3+. The relaxometric properties of these samples are slightly better than the properties of commercial [Gd(DTPA)]2 (DTPA = diethylenetriaminepentaacetate). When taken up by RAW 264.7 cells (mouse macrophage cell line), such bimodal probes exhibit both T1‐weighted MRI increased contrast and fluorescence tracking.

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Stimulation of adult neurogenesis by targeting the endogenous neural stem cells (NSCs), located in hippocampus and subventricular zone (SVZ), with nanoformulations has been proposed for brain repair in cases of neurodegenerative diseases. Unfortunately, it is relatively unknown the nanoformulation properties to facilitate their accumulation in the neurogenic niches after intravenous injection. Here, we have screened different gold-based formulations having variable morphology, surface chemistry and responsiveness to light for their capacity to cross the blood brain barrier (BBB) and accumulate preferentially in the neurogenic niches. Results obtained in a human in vitro BBB model showed that gold nanoparticles (Au NPs) and gold nanorods (Au NRs) conjugated with medium density of transferrin (Tf) peptides (i.e. between 169 and 230 peptides per NP) crossed more efficiently the BBB than the remaining formulations. This is due to a relatively lower avidity of these formulations to Tf receptor (TfR) and lower accumulation in the lysosomes, as compared to the other formulations. We further show that the near infrared light (NIR) irradiation of Au NRs, under a certain concentration and at specific cell culture time, lead to the opening of the BBB. Finally, we demonstrate that Au NRs conjugated with Tf administered intravenously in mice and activated by NIR had the highest accumulation in the neurogenic niches. Our results open the possibility of targeting more effectively the neurogenic niches by controlling the properties of the nanoformulations.

Spatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here, we report a formulation composed of upconversion nanoparticles conjugated with Cre recombinase enzyme through a photocleavable linker, and a lysosomotropic agent that facilitates endolysosomal escape. This formulation allows in vitro spatial control in gene editing after activation with near-infrared light. We further demonstrate the potential of this formulation in vivo through three different paradigms: (i) gene editing in neurogenic niches, (ii) gene editing in the ventral tegmental area to facilitate monitoring of edited cells by precise optogenetic control of reward and reinforcement, and (iii) gene editing in a localized brain region via a noninvasive administration route (i.e., intranasal).

A combination of sol-gel synthesis and thermal decomposition was developed for preparing nanosized, perovskite-type LnFeO 3 (Ln = Eu, Gd, Tb) powders. Perovskite-type powders with crystalline particles of 100 nm average size, as determined by transmission electron microscopy (TEM), could be obtained after a thermal treatment at 800°C. The perovskite nanoparticles (NPs) were further characterized by X-ray powder diffraction and Mössbauer spectroscopy. These were in agreement with the pure perovskite LnFeO 3 structure with the expected Zeeman sextet corresponding to a magnetically ordered [a]