Water soluble, multifunctional antibody-porphyrin gold nanoparticles for targeted photodynamic therapy

Photodynamic therapy (PDT) is a treatment of cancer by which tumour cells are destroyed using reactive oxygen species produced by photosensitizers following activation with visible or near infrared light. Successful PDT depends on the solubility and the targeting ability of the photosensitizers. In this work, the synthesis of a porphyrin-based water soluble nanoparticle conjugate containing a targeting agent that recognizes the erbB2 receptor overexpressed on the surface of particular cancer cells is reported. The nanoparticle conjugates were synthesized following two different protocols, viz. a biphasic and a monophasic method, with the aim to determine which method yielded the optimal nanosystem for potential PDT applications. The nanoparticles were characterized using UV–Vis absorption and fluorescence spectroscopies together with transmission electron microscopy and zeta potential measurements; and their ability to produce singlet oxygen following irradiation was investigated following the decay in absorption of a singlet oxygen probe. The nanoparticles synthesized using the monophasic method were shown to produce the highest amount of singlet oxygen and were further functionalized with anti-erbB2 antibody to target the erbB2 receptors expressed on the surface of SK-BR-3 human breast cancer cells. The water soluble, antibody-porphyrin nanoparticle conjugates were shown to elicit targeted PDT of the breast cancer cells

pRb2/p130 localized to the Cytoplasm in Diffuse Gastric Cancer

pRb2/p130 is a key tumor suppressor, whose oncosuppressive activity has mainly been attributed to its ability to negatively regulate cell cycle by interacting with the E2F4 and E2F5 transcription factors. Indeed, pRb2/p130 has been found altered in various cancer types in which it functions as a valuable prognostic marker. Here, we analyzed pRb2/p130 expression in gastric cancer tissue samples of diffuse histotype, in comparison with their normal counterparts. We found a cytoplasmic localization of pRb2/p130 in cancer tissue samples, whereas, in normal counterparts, we observed the expected nuclear localization. pRb2/p130 cytoplasmic delocalization can lead to cell cycle deregulation, but considering the emerging involvement of pRb2/p130 in other key cellular processes, it could contribute to gastric tumorigenesis also through other mechanisms. Our data support the necessity of further investigations to verify the possibility of using pRb2/p130 as a biomarker or potential therapeutic target for diffuse gastric cancer

Synthesis and in vitro phototoxicity of multifunctional Zn(II)meso-tetrakis(4-carboxyphenyl)porphyrin-coated gold nanoparticles assembled via axial coordination with imidazole ligands

Hypothesis Metalloporphyrins are extensively investigated for their ability to form reactive oxygen species and as potent photosensitisers for use in photodynamic therapy. However, their hydrophobicity generally causes solubility issues concerning in vivo delivery due to lack of distribution and low clearance from the body. Immobilising porphyrins on carriers, such as gold nanoparticles (GNP), can overcome some of these drawbacks. The mode of assembling the porphyrins to the carrier influences the properties of the resulting drug delivery systems. Experiments We describe the synthesis and characterisation of new porphyrin decorated water soluble GNP and we explore Zn-imidazole axial coordination as the mode of linking the porphyrin to the metallic core of the nanoparticles. Quantification of singlet oxygen production, toxicity in dark, cellular uptake by SK-BR-3 cells and phototoxicity have been assessed. Findings Axial coordination limits the number of porphyrins on the gold surface, reduces the formation of aggregates, and diminishes metal exchange in the porphyrin, all of which contribute to enhance the efficiency of singlet oxygen generation from the immobilised porphyrin. In vitro experiments on SK-BR-3 cells reveal a fast uptake followed by more than 80% cell death after irradiation with low doses of light

Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer

Gold nanoparticles (AuNPs) have been extensively studied within biomedicine due to their biocompatibil- ity and low toxicity. In particular, AuNPs have been widely used to deliver photosensitiser agents for photodynamic therapy (PDT) of cancer. Here we review the state-of-the-art for the functionalisation of the gold nanoparticle surface with both photosensitisers and targeting ligands for the active targeting of cancer cell surface receptors. From the initial use of the AuNPs as a simple carrier of the photosensitiser for PDT, the field has significantly advanced to include: the use of PEGylated modification to provide aqueous compatibility and stealth properties for in vivo use; gold metal-surface enhanced singlet oxygen generation; functionalisation of the AuNP surface with biological ligands to specifically target over- expressed receptors on the surface of cancer cells and; the creation of nanorods and nanostars to enable combined PDT and photothermal therapies. These versatile AuNPs have significantly enhanced the efficacy of traditional photosensitisers for both in vitro and in vivo cancer therapy. From this review it is apparent that AuNPs have an important future in the treatment of cancer

Damage to the wood of forest species caused by the debarking of Pallas´s squirrel introduced into Argentina

Aim of study: Pallas´s squirrel (Callosciurus erythraeus) is a harmful and generalist invasive mammal species that causes different problems in the forestry sector. The aim of this study was to evaluate the damage on the wood in three commercial tree species in Argentina, Eucalyptus dunnii, Populus deltoides and Pinus elliottii, due to debarking caused by this squirrel species. Area of study: ¨Liebres Fue¨ forest plantation, located in Luján District (Province of Buenos Aires, Argentina). Material and methods: We analyzed affected tissues and internal defects of wood associated with debarking signs. We randomly collected 74 stems of the three forest species with (N=62) and without debarking (N=12) between October 2016 and December 2017. Transversal cuttings (N=37) and longitudinal cuttings (N=37) of the stems were analyzed. Main results: The defects inside the wood related to the damage due to the debarking caused by Pallas´s squirrels are described. All the damaged samples presented affected wood tissues, with unfavorable healing forming ribbed cracks and ram`s horn scars and/or presence of some internal defect (crack, crack with abnormal coloration, crack with kino/resin or crack with bark included). None of the damaged pieces, according to the rules of visual classification of sawn woods, showed the highest quality grade (Premium). Research highlight: Pallas´s squirrel action causes wounds on the trees, leading to different responses by the trees that are transferred internally, showing abnormalities in the wood which diminish its value from a commercial point of view

Incoherent SAC OCDMA System at 7×622Mbps

Abstract: We demonstrate experimentally an incoherent spectral amplitude coding OCDMA system with seven simultaneous users. BER better than 5×10-6 at 622Mbps is reported for a fully loaded network; errorfree transmission is obtained for five simultaneous users. © 2006 Optical Society of America OCIS codes: (060.2330) Fiber optics communications; (230.1480) Bragg reflector

Taming nuclear complexity with a committee of deep neural networks

We demonstrate that a committee of deep neural networks is capable of predicting the ground-state and excited energies of more than 1800 atomic nuclei with an accuracy akin to the one achieved by state-of-the-art nuclear energy density functionals (EDFs) and a major speed-up. An active learning strategy is proposed to train this algorithm with a minimal set of 210 nuclei. This approach enables future fast studies of the influence of EDFs parametrizations on structure properties over the whole nuclear chart and suggests that for the first time an artificial intelligence successfully encoded the laws of nuclear deformation

Quaternary Stereogenic Carbons in Complex Molecules by an Asymmetric, Organocatalytic, Triple Cascade Reaction

A novel organocatalytic triple cascade that allows the stereoselective construction of all-carbon quaternary sterogenic centers in complex organic molecules has been disclosed. The method provides a flexible and direct access to cyclohexene carbaldehydes with three or four stereogenic carbon atoms with high diastereomeric and complete enantiomeric control, and can be extended to the preparation of enantiopure cyclohexanes with five chiral centers and two quaternary carbons