Julien Boudon

Size exclusion chromatography for semipreparative scale separation of Au38(SR)24 and Au40(SR)24 and larger clusters.

Size exclusion chromatography (SEC) on a semipreparative scale (10 mg and more) was used to size-select ultrasmall gold nanoclusters (<2 nm) from polydisperse mixtures. In particular, the ubiquitous byproducts of the etching process toward Au(38)(SR)(24) (SR, thiolate) clusters were separated and gained in high monodispersity (based on mass spectrometry). The isolated fractions were characterized by UV-vis spectroscopy, MALDI mass spectrometry, HPLC, and electron microscopy. Most notably, the separation of Au(38)(SR)(24) and Au(40)(SR)(24) clusters is demonstrated.

Nanoparticles functionalised with an anti-platelet human antibody for in vivo detection of atherosclerotic plaque by magnetic resonance imaging

UNLABELLED Atherosclerosis is an inflammatory disease associated with the formation of atheroma plaques likely to rupture in which platelets are involved both in atherogenesis and atherothrombosis. The rupture is linked to the molecular composition of vulnerable plaques, causing acute cardiovascular events. In this study we propose an original targeted contrast agent for molecular imaging of atherosclerosis. Versatile USPIO (VUSPIO) nanoparticles, enhancing contrast in MR imaging, were functionalised with a recombinant human IgG4 antibody, rIgG4 TEG4, targeting human activated platelets. The maintenance of immunoreactivity of the targeted VUSPIO against platelets was confirmed in vitro by flow cytometry, transmission electronic and optical microscopy. In the atherosclerotic ApoE(-/-) mouse model, high-resolution ex vivo MRI demonstrated the selective binding of TEG4-VUSPIO on atheroma plaques. It is noteworthy that the rationale for targeting platelets within atherosclerotic lesions is highlighted by our targeted contrast agent using a human anti-αIIbβ3 antibody as a targeting moiety. FROM THE CLINICAL EDITOR Current clinical assessment of atherosclerotic plagues is suboptimal. The authors in the article designed functionalized superparamagnetic iron oxide nanoparticles with TEG4, a recombinant human antibody, to target activated platelets. By using MRI, these nanoparticles can be utilized to study the process of atheroma pathogenesis.

Phthalocyanine–titanate nanotubes: a promising nanocarrier detectable by optical imaging in the so-called imaging window

TiONts–phthalocyanine nanohybrids combining an efficient optical probe and a promising nanovector have been developed in a step-by-step approach and were thoroughly characterized. Each 150 nm long TiONts–Pc bear ca. 450 Pc. Three nanohybrids were prepared including three different linkers in quest for the best stability.

DNA structure-specific sensitization of a metalloporphyrin leads to an efficient in vitro quadruplex detection molecular tool

The search for convenient molecular probes for detecting DNA and RNA quadruplexes in vitro is marked by a rapid pace of progress, spurred on by the multiple roles these higher-order nucleic acid structures play in many genetic dysregulations. Here, we contribute to this search, reporting on a palladated porphyrin named Pd·TEGPy: its efficiency as quadruplex-selective fluorescent dye relies on a structural design that endows it with attractive supramolecular and electronic properties and makes it an efficient turn-on, quadruplex-selective fluorescent stain thanks to a DNA-mediated sensitization mechanism that ensures a high level of specificity.

Docetaxel-titanate nanotubes enhance radiosensitivity in an androgen-independent prostate cancer model

Around 40% of high-risk prostate cancer patients who undergo radiotherapy (RT) will experience biochemical failure. Chemotherapy, such as docetaxel (DTX), can enhance the efficacy of RT. Multidrug resistance mechanisms often limit drug efficacy by decreasing intracellular concentrations of drugs in tumor cells. It is, therefore, of interest to develop nanocarriers of DTX to maintain the drug inside cancer cells and thus improve treatment efficacy. The purpose of this study was to investigate the use of titanate nanotubes (TiONts) to develop a TiONts-DTX nanocarrier and to evaluate its radiosensitizing in vivo efficacy in a prostate cancer model. In vitro cytotoxic activity of TiONts-DTX was evaluated using an MTS assay. The biodistribution of TiONts-DTX was analyzed in vivo by single-photon emission computed tomography. The benefit of TiONts-DTX associated with RT was evaluated in vivo. Eight groups with seven mice in each were used to evaluate the efficacy of the nanohybrid combined with RT: control with buffer IT injection ± RT, free DXL ± RT, TiONts ± RT and TiONts-DXL ± RT. Mouse behavior, health status and tumor volume were monitored twice a week until the tumor volume reached a maximum of 2,000 mm3. More than 70% of nanohybrids were localized inside the tumor 96 h after administration. Tumor growth was significantly slowed by TiONts-DTX associated with RT, compared with free DTX in the same conditions (P=0.013). These results suggest that TiONts-DTX improved RT efficacy and might enhance local control in high-risk localized prostate cancer.

Taxane-Grafted Metal-Oxide Nanoparticles as a New Theranostic Tool against Cancer: The Promising Example of Docetaxel-Functionalized Titanate Nanotubes on Prostate Tumors

The combination of anticancer drugs and metal oxide nanoparticles is of great interest in cancer nanomedicine. Here, the development of a new nanohybrid, titanate nanotube-docetaxel (TiONts-DTX) is reported, the two parts of which are conjugated by covalent linkages. Unlike most nanoparticles currently being developed for biomedical purposes, TiONts present a needle-shaped morphology. The surface of TiONts is linked with 3-aminopropyl triethoxysilane and with a hetero-bifunctional polymer (polyethylene glycol) to create well-dispersed and biocompatible nanovectors. The prefunctionalized surface of this scaffold has valuable attachments to graft therapeutic agents (DTX in our case) as well as chelating agents (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) to monitor the nanohybrids. To evaluate drug efficacy, in vitro tests have demonstrated that the association between TiONts and DTX shows cytotoxic activity against a hormone-refractory prostate cancer cell line (22Rv1) whereas TiONts without DTX do not. Finally, the first in vivo tests with intratumoral injections show that more than 70% of TiONts nanovectors are retained within the tumor for at least 7 d. Moreover, tumor growth in mice receiving TiONts-DTX is significantly slower than that in mice receiving free DTX. This nanohybrid can thus become a promising new tool in biomedicine to fight against prostate cancer.

Probing chiral nanoparticles and surfaces by infrared spectroscopy

Chiral metal surfaces and nanoparticles have the potential to be used for the selective production, the resolution and the detection of enantiomers of a chiral compound, which renders them highly attractive in view of the tremendous consequences of homochirality on earth. Their capability to distinguish between enantiomers of a chemical compound relies on their structure and the ability to form intermolecular interactions. However, molecular-level understanding of the interactions that are at the origin of enantiodiscrimination is lagging behind due to the lack of powerful experimental techniques that are able to spot these interactions selectively with high sensitivity. In this article two techniques based on infrared spectroscopy are presented that are able to selectively target the chiral properties of nanoparticles and interfaces. These are the combination of attenuated total reflection infrared (ATR-IR) with modulation excitation spectroscopy (MES) to probe enantiodiscriminating interactions at chiral solid-liquid interfaces and vibrational circular dichroism (VCD), which is used to probe the structure of chirally modified metal nanoparticles.

In vitro interaction and biocompatibility of titanate nanotubes with microglial cells

&NA; Titanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3‐aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV‐2 cells. TiONts‐APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV‐2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts‐APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts‐APTES exhibited good biocompatibility on microglial BV‐2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis. Graphical abstract (3‐aminopropyl) triethoxysilane (APTES) functionalized titanate nanotubes (named TiONts on the scheme) enter the BV‐2 cell both via endocytosis and passive diffusion. Inside cell, TiONts‐APTES are capable of inducing superoxide radicals which later get converted to peroxides by SOD activity. TiONts‐APTES interact with mitochondria to induce a transient increase in &Dgr;&PSgr;m which further gives way to mitochondria mediated ROS production. TiONts‐APTES do not affect lysosomal integrity or cell cycle pattern. At high concentration TiONts‐APTES probably induce caspase‐mediated apoptosis in BV‐2 cells leading to PARP cleavage. Figure. No Caption available. HighlightsSpiral‐shaped titanate nanotubes functionalized with APTES exhibit good colloidal stability.Nanotubes exposure does not result in morphological alteration or cytotoxicity in BV2 cells.Increase in mitochondrial membrane potential and ROS production post exposure is short lived.Nanotubes exposure does not induce microglial activation in BV2 cells.Slight reduction in cell viability at high concentrations is mediated by apoptosis.

Cellular interactions of functionalized superparamagnetic iron oxide nanoparticles on oligodendrocytes without detrimental side effects: Cell death induction, oxidative stress and inflammation

Iron oxide nanoparticles have the capability to cross Blood Brain Barrier (BBB) and hence are widely investigated for biomedical operations in the central nervous system. Before being used for the biomedical purpose, it is necessary to investigate its biocompatibility, dosimetry and biological interaction. In the present study, in-house synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were functionalized using the polymer, PolyEthylene Glycol (PEG) and a fluorophore (Rhodamine). The interaction of these nanoparticles with murine oligodendrocytes 158N was studied using different assays. The nanoparticles were taken up by the cells via endocytosis and there was a dose-dependent increase in the intracellular iron content as revealed by flow cytometry, transmission electron microscopy and confocal microscopy. Nanoparticles remained stable inside cells even after 24 h. Cell sorting capacity using a magnet depended on the number of particles interact per cell. SPIONs exhibited good biocompatibility as no toxicological responses, including morphological changes, loss of viability, oxidative stress or inflammatory response (IL-1β, IL-6 secretion) were observed. Together, these data show that the in-house synthesized SPIONs have no side effects on 158N cells, and constitute interesting tools for biomedical applications across brain, including cellular imaging and targeting.