Exhibiting a red-shifted absorption/scattering feature compared to conventional plasmonic metals, titanium nitride nanoparticles (TiN NPs) look as very promising candidates for biomedical applications, but these applications are still underexplored despite the presence of extensive data for conventional plasmonic counterparts. Here, we report the fabrication of ultrapure, size-tunable TiN NPs by methods of femtosecond laser ablation in liquids and their biological testing. We show that TiN NPs demonstrate strong and broad plasmonic peak around 640–700 nm with a significant tail over 800 nm even for small NPs sizes (<7 nm). In vitro tests of laser-synthesized TiN NPs on cellular models evidence their low cytotoxicity and excellent cell uptake. We finally demonstrate a strong photothermal therapy effect on U87–MG cancer cell cultures using TiN NPs as sensitizers of local hyperthermia under near-infrared laser excitation. Based on absorption band in the region of relative tissue transparency and acceptable biocompatibility, laser-synthesized TiN NPs promise the advancement of biomedical modalities employing plasmonic effects, including absorption/scattering contrast imaging, photothermal therapy, photoacoustic imaging and SERS.

The management of brain diseases remains a challenge, particularly because of the difficulty for drugs to cross the blood–brain barrier. Among strategies developed to improve drug delivery, nano-sized emulsions (i.e., nanoemulsions), employed as nanocarriers, have been described. Moreover, focused ultrasound-mediated blood–brain barrier disruption using microbubbles is an attractive method to overcome this barrier, showing promising results in clinical trials. Therefore, nanoemulsions combined with this technology represent a real opportunity to bypass the constraints imposed by the blood–brain barrier and improve the treatment of brain diseases. In this work, a stable freeze-dried emulsion of perfluorooctyl bromide nanodroplets stabilized with home-made fluorinated surfactants able to carry hydrophobic agents is developed. This formulation is biocompatible and droplets composing the emulsion are internalized in multiple cell lines. After intravenous administration in mice, droplets are eliminated from the bloodstream in 24 h (blood half-life (t_1/2) = 3.11 h) and no long-term toxicity is expected since they are completely excreted from mice’ bodies after 72 h. In addition, intracerebral accumulation of tagged droplets is safely and significantly increased after focused ultrasound-mediated blood–brain barrier disruption. Thus, the proposed nanoemulsion appears as a promising nanocarrier for a successful focused ultrasound-mediated brain delivery of hydrophobic agents.

Highly water-soluble, nontoxic organic nanoparticles on which paclitaxel (PTX), a hydrophobic anticancer drug, has been covalently bound via an ester linkage (4.5% of total weight) have been prepared for the treatment of glioblastoma. These soft fluorescent organic nanoparticles (FONPs), obtained from citric acid and diethylenetriamine by microwave-assisted condensation, show suitable size (Ø = 17–30 nm), remarkable solubility in water, softness as well as strong blue fluorescence in an aqueous environment that are fully retained in cell culture medium. Moreover, these FONPs were demonstrated to show in vitro safety and preferential internalization in glioblastoma cells through caveolin/lipid raft-mediated endocytosis. The PTX-conjugated FONPs retain excellent solubility in water and remain stable in water (no leaching), while they showed anticancer activity against glioblastoma cells in two-dimensional and three-dimensional culture. PTX-specific effects on microtubules reveal that PTX is intracellularly released from the nanocarriers in its active form, in relation with an intracellular-promoted lysis of the ester linkage. As such, these hydrophilic prodrug formulations hold major promise as biocompatible nanotools for drug delivery.

Background: Recent research has demonstrated the potential of 18-kDa translocator protein (TSPO) to serve as a target for nuclear imaging of gliomas. The aim of this study was to evaluate SPECT imaging of GL26 mouse glioma using radioiodinated CLINDE, a TSPO-specific tracer. Methods: GL26 cells, previously transfected with an enhanced green fluorescent protein (EGFP)-expressing lentivirus, were stereotactically implanted in the striatum of C57/Bl6 mice. At 4 weeks post-injection, dynamic SPECT scans with [¹²³I]CLINDE were performed. A displacement study assessed specificity of tracer binding. SPECT images were compared to results of autoradiography, fluorescence microscopy, in situ nucleic acid hybridization, histology, and immunohistochemistry. Western blotting was performed to verify TSPO production by the tumor. Results: Specific uptake of tracer by the tumor is observed with a high signal-to-noise ratio. Tracer uptake by the tumor is indeed 3.26 ± 0.32 times higher than that of the contralateral striatum, and 78% of the activity is displaceable by unlabeled CLINDE. Finally, TSPO is abundantly expressed by the GL26 cells. Conclusions: The present study demonstrates the feasibility of [¹²³I]CLINDE SPECT in translational studies and underlines its potential for clinical glioma SPECT imaging.