α-sarcin and RNase T1 based immunoconjugates: the role of intracellular trafficking in cytotoxic efficiency

Toxins have been thoroughly studied for their use as therapeutic agents in search of an improvement in toxic efficiency together with a minimization of their undesired side effects. Different studies have shown how toxins can follow different intracellular pathways which are connected with their cytotoxic action inside the cells. The work herein presented describes the different pathways followed by the ribotoxin a-sarcin and the fungal RNase T1,as toxic domains of immunoconjugates with identical binding domain, the single chain variable fragment of a monoclonal antibody raised against the glycoprotein A33. According to the results obtained both immunoconjugates enter the cells via early endosomes and, while a-sarcin can translocate directly into the cytosol to exert its deathly action, RNase T1 follows a pathway that involves lysosomes and the Golgi apparatus. These facts contribute to explaining the different cytotoxicity observed against their targeted cells, and reveal how the innate properties of the toxic domain, apart from its catalytic features, can be a key factor to be considered for immunotoxin optimization.

Optimized square Fresnel zone plates for microoptics applications

Polygonal Fresnel zone plates with a low number of sides have deserved attention in micro and nanoptics, because they can be straightforwardly integrated in photonic devices, and, at the same time, they represent a balance between the high-focusing performance of a circular zone plate and the easiness of fabrication at micro and nano-scales of polygons. Among them, the most representative family are Square Fresnel Zone Plates (SFZP). In this work, we propose two different customized designs of SFZP for optical wavelengths. Both designs are based on the optimization of a SFZP to perform as close as possible as a usual Fresnel Zone Plate. In the first case, the criterion followed to compute it is the minimization of the difference between the area covered by the angular sector of the zone of the corresponding circular plate and the one covered by the polygon traced on the former. Such a requirement leads to a customized polygon-like Fresnel zone. The simplest one is a square zone with a pattern of phases repeating each five zones. On the other hand, an alternative SFZP can be designed guided by the same criterion but with a new restriction. In this case, the distance between the borders of different zones remains unaltered. A comparison between the two lenses is carried out. The irradiance at focus is computed for both and suitable merit figures are defined to account for the difference between them.