Editorial: Cancer Nanotheranostics: What Have We Learned So Far?

According to the National Cancer Institute, in 2015 an estimated of 1.7 million new cases of cancer will be diagnosed only in the United States and around 600, 000 people will die from the disease. The most common type of cancer is breast cancer, with more than 234, 000 new cases expected in the United States in 2015. The next most common cancers are prostate cancer and lung cancer.After a quarter of century of rapid technological advances, research has revealed the complexity of cancer, a disease intimately related to the dynamic transformation of the genome. These transformations trigger a range of modification to cell processes and molecular events that initiate and promote tumor genesis and progression, then local invasion and metastasis, i.e., the hallmarks of cancer development. These alterations may cause a wide scope of “diseases” that share similar molecular patterns that cause transformation and malignancy. Each of this stepwise evolution of the initial molecular event drives abnormal growth and loss of differentiation that ultimately causes tissue and organ failure. The initial molecular event may lay within the erroneous expression of a given gene, epigenetic modification and/or sporadic mutations occurring on genomic DNA during the life span of organisms. Each and every one of these molecular events may be evaluated and used as diagnostics biomarker and therapeutic target. For example, therapy action may target a mutated gene and silence its expression so as to avoid erroneous protein expression that mutates cell function. However, the full understanding of the molecular onset of this disease is still far from achieved and the search for mechanisms of treatment will follow closely..

Effective in Vitro Photokilling by Cell-Adhesive Gold Nanorods

Upon excitation of their localized surface plasmon resonance (LSPR) band, gold nanorods (AuNRs) show a characteristic light-to-heat transduction, a useful and versatile property for a range of biomedical applications such as photothermal therapy, drug delivery, optoacoustic imaging and biosensing, among others. Nanoparticle (NP)-mediated photothermal therapy (PTT) rests on the ability of nanomaterials to convert light energy into heat and can currently be considered as a promising method for selectively destroying tumor cells by (photo)-thermoablation. One inherent limitation to NP-mediated PTT is that the nanoparticles must arrive at the site of action to exert their function and this typically involves cellular internalization. Here we report the use of the Keggin-type polyoxometalate (POM) phosphotungstic acid (PTA) as an inorganic gelling agent for the encapsulation of plasmonic gold nanorods (AuNRs) inside a biocompatible and cell-adhesive chitosan hydrogel matrix. These functional sub-micrometric containers are non-cytotoxic and present the ability to adhere to the cytoplasmic membranes of cells avoiding any need for cellular internalization, rendering them as highly efficient thermoablating agents of eukaryotic cells in vitro

Liner radius fluctuations in a high-gain Cherenkov free-electron laser

Phase shifts in the propagating electromagnetic field of a Cherenkov free-electron laser (CFEL) can affect its gain. The phase velocity of an electromagnetic wave varies, for example, when the lined waveguide is inhomogeneous along its length. In this paper, we study quantitatively the saturated power of a particular CFEL at both weak and strong electron-beam pumping when the inner radius of the liner contains fluctuations along the waveguide. We show that the gain bandwidth of the CFEL is substantially broadened when the CFEL is pumped with a high-current beam. We also show that the design of a CFEL needs to include optimization with respect to sensitivity to liner fluctuations, especially for weakly pumped CFELs, that is, CFELs that use a low-current electron-beam density. This optimization can be relaxed for more strongly pumped CFELs

Study of urgent visits to commercial rabbit farms in Spain and Portugal during 1997-2007

[EN] This is a report on work carried out on 4307 visits to 868 commercial farms with domestic rabbits in Spain and Portugal from January 1997 to December 2007. Of the total visits, 2237 (52%) were emergencies on 660 farms. The median size of the farms ranged between 450 does in 1997 and 750 in 2007. This retrospective study measures the clinical disease occurrence using the Monthly Risk of urgent visits (MR), i.e. the percentage of visits made as a result of each clinical disease in comparison with the total number of urgent visits made each month. The main reasons for the emergencies were mucoid enteropathy (similar to Epizootic Rabbit Enteropathy), with a MR: 25.0%, enteritis-diarrhoea (24.1%), myxomatosis, (11.1%), reproductive troubles (8.6%), respiratory diseases (7.2%) and staphylococcosis (4.2%). Fifty-four percent of the urgent visits were due to diseases of the digestive system. Mucoid enteropathy was still one of the main diseases faced by the commercial rabbit industry during the study period. No significant yearly or monthly variations were observed in the analysis of the MR. A seasonal effect was only found in respiratory diseases during the summer (MR: 11.06±0.01) and myxomatosis in autumn (MR: 14.60±0.02), in comparison with spring (MR: 7.44±0.02). It is therefore concluded that farms should be permanently protected as they might be affected by any of these diseases at any time during the year.Rosell, J.; Fuente, LDL.; Badiola, J.; Fernández De Luco, D.; Casal, J.; Saco, M. (2009). Study of urgent visits to commercial rabbit farms in Spain and Portugal during 1997-2007. World Rabbit Science. 17(3):127-136. doi:10.4995/wrs.2009.65212713617

Variaciones temporales del contenido en ácidos grasos de leche de oveja

El presente trabajo ha consistido en la estimación de la repetibilidad tem- poral diaria, semanal y mensual, del contenido de los ácidos grasos de la leche de oveja en el curso de una lactación. Se ha realizado la cuantificación para 36 ácidos grasos y 6 agrupaciones en 596 muestras de leche procedente de 32 ovejas de las razas Churra y Assaf. Las bajas repetibilidades, en aquellos ácidos con muy baja concentración, son debido a un efecto de falta de precisión en su cuantificación, originado por el bajo contenido de dicho ácido graso. La concentración de ácidos grasos en la leche ovina, presenta una variación a lo largo de la lactación que es proporcional a las distancia entre controles. Para las variables cuantitativamente importantes, las repetibilidades medias diarias, semanales y mensuales fueron 0,55, 0,46 y 0,32 respectivamente

Polypeptidic Micelles Stabilized with Sodium Alginate Enhance the Activity of Encapsulated Bedaquiline

The coating of polypeptidic micelles with sodium alginate is described as a strategy to improve the stability of micelles for drug delivery. Bedaquiline, approved in 2012 for the treatment of multidrug resistant tuberculosis, has been used as an example of hydrophobic drug to study the loading efficiency, the release of the encapsulated drug in different media, and the in vitro antimicrobial activity of the system. Alginate coating prevents the burst release of the drug from micelles upon dilution and leads to a sustained release in all tested media. In view of possible oral administration, the alginate coated micelles show better stability in gastric and intestinal simulated media. Notably, the encapsulated bedaquiline shows increased in vitro activity against Mycobacterium tuberculosis compared to free bedaquiline

Design of stable magnetic hybrid nanoparticles of Si-entrapped HRP

Hybrid and composite nanoparticles represent an attractive material for enzyme integration due to possible synergic advantages of the structural builders in the properties of the nanobiocatalyst. In this study, we report the synthesis of a new stable hybrid nanobiocatalyst formed by biomimetic silica (Si) nanoparticles entrapping both Horseradish Peroxidase (HRP) (EC 1.11.1.7) and magnetic nanoparticles (MNPs). We have demonstrated that tailoring of the synthetic reagents and post immobilization treatments greatly impacted physical and biocatalytic properties such as an unprecedented ~280 times increase in the half-life time in thermal stability experiments. The optimized nanohybrid biocatalyst that showed superparamagnetic behaviour, was effective in the batch conversion of indole-3-acetic acid, a prodrug used in Direct Enzyme Prodrug Therapy (DEPT). Our system, that was not cytotoxic per se, showed enhanced cytotoxic activity in the presence of the prodrug towards HCT-116, a colorectal cancer cell line. The strategy developed proved to be effective in obtaining a stabilized nanobiocatalyst combining three different organic/inorganic materials with potential in DEPT and other biotechnological applications

Enhancing Luminescence and X-ray Absorption Capacity of Eu3+:LaF3 Nanoparticles by Bi3+ Codoping

Bi3+ codoping has been proposed in this work with a twofold objective, namely, enhancing the luminescence emission of Eu3+:LaF3 nanoparticles (NPs) and increasing their X-ray attenuation capacity, with the purpose of obtaining a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography. The synthesis method, reported here for the first time for LaF3 particles, allowed obtaining uniform, nonaggregated NPs using a homogeneous precipitation in polyol medium at room temperature in just 2 h. The simplicity of the synthesis method allows the large-scale production of NPs. LaF3 NPs with different Eu3+ contents were first synthesized to find the critical Eu3+ concentration, producing the highest emission intensity. This concentration was subsequently used to fabricate Bi3+-Eu3+-codoped LaF3 NPs using the same method. The emission intensity of the codoped NPs increased in more than one order of magnitude, thanks to the possibility of excitation through the Bi3+ ¿ Eu3+ energy-transfer band. The luminescence properties of the codoped NPs were analyzed in detail to find the mechanism responsible for the emission enhancement. Finally, it was demonstrated that the high atomic number of Bi3+, higher than that of lanthanides, was an added value of the material because it increased its X-ray attenuation capacity. In summary, the LaF3 NPs codoped with Eu3+ and Bi3+ presented in this work are promising candidates as a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography

Highly efficient t2 cobalt ferrite nanoparticles vectorized for internalization in cancer cells

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in the structure. A stable and biocompatible targeting conjugate nanoparticle-folic acid (NP-FA) was developed that was capable of targeting FA receptor positivity in HeLa (human cervical cancer) cancer cells. The biocompatibility of NP-FA was assessed in vitro in HeLa cells using the MTT assay, and morphological analysis of the cytoskeleton was performed. A high level of NP-FA binding to HeLa cells was confirmed through qualitative in vitro targeting studies. A value of 479 Fe+Co mM-1s-1 of transverse relaxivity (r2 ) was obtained in colloidal suspension. In addition, in vitro analysis in HeLa cells also showed an important effect in negative T2 contrast. Therefore, the results show that NP-FA can be a potential biomaterial for use in bio medical trials, especially as a contrast agent in magnetic resonance imaging (MRI)