Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain.

High-resolution solution NMR spectroscopy has been used to characterize the structure of Pd dendrimer-encapsulated nanoparticles (DENs), consisting of approximately 55-atom nanoparticles encapsulated within fourth-generation, hydroxyl-terminated poly(amidoamine) PAMAM dendrimers (G4-OH). Detailed analysis of 1D and 2D NMR spectra of dendrimers with (G4-OH(Pd(55))) and without (G4-OH) nanoparticles unambiguously demonstrate that single nanoparticles are encapsulated within individual dendrimers. This conclusion is based on the following results. First, the NMR data show that signals arising from the innermost methylenes of G4-OH(Pd(55)) are more highly influenced by the presence of the Pd nanoparticles than are the terminal functional groups. This means that DENs are encapsulated within dendrimers rather than being adsorbed to their surface, as would be the case for aggregates consisting of multiple dendrimers and nanoparticles. Second, extraction of DENs from within their dendrimer hosts results in an increase in the NMR intensity associated with the interior methylenes, which corroborates the previous point. Third, NMR pulse-field gradient spin-echo experiments demonstrate that G4-OH and G4-OH(Pd(55)) have identical hydrodynamic radii, and this finding excludes the presence of dendrimer/nanoparticle aggregates.

High-resolution solution (1)H NMR spectroscopy has been used to characterize the size of Pd dendrimer-encapsulated nanoparticles (DENs). The Pd nanoparticles measured by this technique contain 55, 147, 200, or 250 atoms, and they are encapsulated within sixth-generation, hydroxyl-terminated poly(amidoamine) PAMAM dendrimers (G6-OH). Detailed analysis of the NMR data shows that signals arising from the innermost protons of G6-OH(Pd(n)) decrease significantly as the size of the encapsulated nanoparticles increase. A mathematical correlation between this decrease in the integral value and the theoretical number of Pd atoms in the nanoparticle is extracted. It enables the elucidation of the size of Pd DENs by (1)H NMR spectroscopy. NMR pulse-field gradient spin-echo experiments demonstrate that G6-OH with and without DENs have identical hydrodynamic radii, which excludes the presence of dendrimer/nanoparticle aggregates.

A series of novel 4,4Ј-disubstituted organic-organometallic stilbenes were synthesized, that is, the 4Ј-substituted stil--in which R = C 2 H 2 C 6 H 4 -RЈ-4Ј with RЈ = NMe 2 , OMe, SiMe 3 , H, I, CN, NO 2 ) (1-7). In these compounds the PtCl grouping can be considered to be present as a donor substituent. Their synthesis involved a Horner-Wadsworth-Emmons reaction of [PtCl(NCN-CHO-4)] (9) with the appropriate phosphonate ester derivatives (8a-g). Under these reaction conditions, the C-Pt bond in aldehyde 9 was not affected, and the platinated stilbene products were obtained in 53-90 % yield. The solidstate structures of complexes 1, 2 and 5-7 were determined by single-crystal X-ray diffraction, which revealed interesting bent conformations for 2, 5 and 7. Linear correlations were found between both the 13 C{ 1 H} (C ipso to Pt) and the

The combination of different nanomaterials such as metallic nanoparticles and carbon nanostructures in a new hybrid material should give rise to interesting properties that combine the advantages of each of the nanocomponents. This review highlights the latest advances in the synthetic design of these hybrid materials where carbon nanostructures act as supports as well as stabilizing agents for very reactive metallic nanoparticles. The striking applications of Pd nanoparticles anchored on the surface of carbon nanostructures in C-C coupling chemistry are analyzed. Special emphasis is placed on the stability of these materials, which is linked to their recyclability. Numerous examples are given that involve the use of these catalysts in Heck, Suzuki and Sonogashira coupling reactions.

J. Neurochem. (2012) 120, 515–527. Abstract During excitotoxic neuronal death, Bax translocates to the mitochondria where it plays an important role by contributing to the release of proapoptotic factors. However, how Bax translocates to the mitochondria during excitotoxicity remains poorly understood. Herein, our data suggest the presence of a novel signalling mechanism by which NMDA receptor stimulation promotes Bax translocation. This signalling pathway is triggered by dephosphorylation of cofilin. Once dephosphorylated, cofilin might interact physically with Bax acting as a carrier for it, translocating it to the mitochondria, where it contributes to mitochondrial membrane despolarization, permeabilization and to the release of apoptotic factors, thus leading to neuronal death. Lack‐of‐function studies indicate that only the Slingshot family of phosphatases, more specifically the enzyme Slingshot 1L phosphatase, but not cronophin participates in the cofilin activation process during excitotoxicity. Indeed, cofilin‐mediated Bax translocation seems to be a key event in excitotoxic neuronal death as knock down of either cofilin or Slingshot 1L phosphatase has a marked neuroprotective effect on NMDA‐mediated neuronal death. This novel biochemical pathway may therefore be a good target to develop future therapeutic molecules for neurodegenerative diseases.

A novel hybrid dendrimer (TRANSGEDEN) that combines a conjugated rigid polyphenylenevinylene (PPV) core with flexible polyamidoamine (PAMAM) branches at the surface was synthesized and characterized. The potential of this material as a nonviral gene delivery system was also examined, and it was observed that dendriplexes formed by TRANSGEDEN and small interfering ribonucleic acids (siRNAs) can be incorporated into >90% of neuronal cells without any toxicity up to a dendrimer concentration of 3 μM. TRANSGEDEN was used to deliver a specific siRNA to rat cerebellar granular neurons (CGNs) to knock down the cofilin-1 protein. Cofilin-1 removal partially protects CGNs from N-methyl D-aspartate (NMDA)-mediated neuronal death.

In this paper, we report the functionalization of the surface of multiwalled carbon nanotubes (MWNTs) with Au dendrimer encapsulated nanoparticles (DENs). The results show that, when pristine MWNTs having hydrophobic surfaces are exposed to DENs, the dendrimers aggregate on the MWNT surface. However, when the MWNTs are oxidized in acid prior to exposure to DENs, well-dispersed submonolayer coverages of Au nanoparticles are observed on the MWNT surface. This suggests that acid-induced debundling of the nanotubes is an essential prerequisite for attachment of nearly monodisperse DENs. Electron microscopy and NMR spectroscopy confirm that the structures of the DENs and dendrimers are retained after immobilization on the surface of acid-functionalized MWNTs.