Enhanced neuronal cell differentiation combining biomimetic peptides and a carbon nanotube-polymer scaffold.

Carbon nanotubes are attractive candidates for the development of scaffolds able to support neuronal growth and differentiation thanks to their ability to conduct electrical stimuli, to interface with cells and to mimic the neural environment. We developed a biocompatible composite scaffold, consisting of multi-walled carbon nanotubes dispersed in a poly-L-lactic acid matrix able to support growth and differentiation of human neuronal cells. Moreover, to mimic guidance cues from the neural environment, we also designed synthetic peptides, derived from L1 and LINGO1 proteins. Such peptides could positively modulate neuronal differentiation, which is synergistically improved by the combination of the nanocomposite scaffold and the peptides, thus suggesting a prototype for the development of implants for long-term neuronal growth and differentiation. From the clinical editor: The study describes the design and preparation of nanocomposite scaffolds with multi-walled carbon nanotubes in a poly-L-lactic acid matrix. This compound used in combination with peptides leads to synergistic effects in supporting neuronal cell growth and differentiation.

Synthesis and electronic properties of 1,2-hemisquarimines and their encapsulation in a cucurbit[7]uril host.

The synthesis of a new class of robust squaraine dyes, colloquially named 1,2-hemisquarimines (1,2-HSQiMs), through the microwave-assisted condensation of aniline derivatives with the 1,2-squaraine core is reported. In CH3CN, 1,2-HSQiMs show a broad absorption band with a high extinction coefficient and a maximum at around λ=530 nm, as well as an emission band centered at about λ=574 nm, that are pH dependent. Protonation of the imine nitrogen causes a redshift of both absorption and emission maxima, with a concomitant increase in the lifetime of the emitting excited state. Encapsulation of the chromophore into a cucurbit[7]uril host revealed fluorescence enhancement and increased photostability in water. The redox characteristics of 1,2-HSQiMs indicate that charge injection into TiO2 is possible; this opens up promising perspectives for their use as photosensitizers for solar energy conversion.

Synthesis and characterisation of a trithiocarbonate for the decoration of carbon nanostructures.

A novel aldehyde-bearing trithiocarbonate has been synthesized and reacted with carbon nanostructures with different dimensionalities (nanotubes, fullerenes, graphite). The decoration of these carbon nanostructures with trithiocarbonate moieties should provide a powerful tool for the design of advanced carbon nanofillers.

The continuous-flow cycloaddition of azomethine ylides to carbon nanotubes.

This communication demonstrates a straightforward continuous-flow method for efficient exohedral functionalisation of carbon nanotubes which affords soluble samples in a much shorter time over conventional batch processing.

Electronic interactions between "pea" and "pod": the case of oligothiophenes encapsulated in carbon nanotubes.

One of the most challenging strategies to achieve tunable nanophotonic devices is to build robust nanohybrids with variable emission in the visible spectral range, while keeping the merits of pristine single-walled carbon nanotubes (SWNTs). This goal is realized by filling SWNTs ("pods") with a series of oligothiophene molecules ("peas"). The physical properties of these peapods are depicted by using aberration-corrected high-resolution transmission electron microscopy, Raman spectroscopy, and other optical methods including steady-state and time-resolved measurements. Visible photoluminescence with quantum yields up to 30% is observed for all the hybrids. The underlying electronic structure is investigated by density functional theory calculations for a series of peapods with different molecular lengths and tube diameters, which demonstrate that van der Waals interactions are the bonding mechanism between the encapsulated molecule and the tube.

Photophysics of squaraine dyes: role of charge-transfer in singlet oxygen production and removal.

The unique optical properties of squaraines render these molecules useful for applications that range from xerography to photodynamic therapy. In this regard, squaraines derived from the condensation of nitrogen-based heterocycles and squaric acid have many promising attributes. Key solution-phase photophysical properties of six such squaraines have been characterized in this study. One feature of these molecules is a pronounced absorption band in the region approximately 600-720 nm that has significant spectral overlap with the fluorescence band (i.e., the Stokes shift is small). As such, effects of emission/reabsorption yield unique excitation wavelength dependent phenomena that are manifested in quantum yields of both fluorescence and sensitized singlet oxygen production. Comparatively small squaraine-sensitized yields of singlet oxygen production and, independently, large rate constants for squaraine-induced deactivation of singlet oxygen are consistent with a model in which there is appreciable intra- and intermolecular charge-transfer in the squaraine and squaraine-oxygen encounter complex, respectively. The results reported herein should be useful in the further development of these compounds for a range of oxygen-dependent applications.

Photooxidation and Phototoxicity of pi-extended squaraines.

This paper describes the synthesis of pi-extended squaraines and their photooxidation properties and gives an in-depth characterization of these molecules as photosensitizing agents. Squaraines show a strong absorption in the tissue transparency window (600-800 nm), and upon irradiation, they undergo a photooxidation process, leading to the formation of peroxide and hydroperoxide radicals according to a type I radical chain process. Confocal laser microscopy demonstrates that the designed squaraines efficiently internalize in the cytoplasm and not in the nucleus of the cell. In the dark, they are scarcely cytotoxic, but after irradition, they promote a strong dose-dependent phototoxic effect in four different cancer cells. In HeLa and MCF-7 cells, squaraines 4 and 5, thanks to their hydrocarbon tails, associate to the membranes and induce lipid peroxidation, as indicated by a marked increase of malonyldialdehyde after photodynamic treatment, in agreement with in vitro photooxidation studies. FACS, caspase-3/7 assays and time-lapse microscopy demonstrate that the designed squaraines cause cell death primarily by necrosis.

Assessment of water-soluble pi-extended squaraines as one- and two-photon singlet oxygen photosensitizers: design, synthesis, and characterization.

Singlet oxygen sensitization by organic molecules is a topic of major interest in the development of both efficient photodynamic therapy (PDT) and aerobic oxidations under complete green chemistry conditions. We report on the design, synthesis, biology, and complete spectroscopic characterization (vis-NIR linear and two-photon absorption spectroscopy, singlet oxygen generation efficiencies for both one- and two-photon excitation, electrochemistry, intrinsic dark toxicity, cellular uptake, and subcellular localization) of three classes of innovative singlet oxygen sensitizers pertaining to the family of symmetric squaraine derivatives originating from pi-excessive heterocycles. The main advantage of pi-extended squaraine photosensitizers over the large number of other known photosensitizers is their exceedingly strong two-photon absorption enabling, together with sizable singlet oxygen sensitization capabilities, for their use at the clinical application relevant wavelength of 806 nm. We finally show encouraging results about the dark toxicity and cellular uptake capabilities of water-soluble squaraine photosensitizers, opening the way for clinical small animal PDT trials.