5 research outputs found
Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer
Background: Functionalized nanoparticles (NPs) are one promising tool for detecting specific molecular targets and combine molecular biology and nanotechnology aiming at modern imaging. We aimed at ligand-directed delivery with a suitable target-biomarker to detect early pancreatic ductal adenocarcinoma (PDAC). Promising targets are galectins (Gal), due to their strong expression in and on PDAC-cells and occurrence at early stages in cancer precursor lesions, but not in adjacent normal tissues. Results: Molecular probes (10-29 AA long peptides) derived from human tissue plasminogen activator (t-PA) were selected as binding partners to galectins. Affinity constants between the synthesized t-PA peptides and Gal were determined by microscale thermophoresis. The 29 AA-long t-PA-peptide-1 with a lactose-functionalized serine revealed the strongest binding properties to Gal-1 which was 25-fold higher in comparison with the native t-PA protein and showed additional strong binding to Gal-3 and Gal-4, both also over-expressed in PDAC. t-PA-peptide-1 was selected as vector moiety and linked covalently onto the surface of biodegradable iron oxide nanoparticles (NPs). In particular, CAN-doped maghemite NPs (CAN-Mag), promising as contrast agent for magnetic resonance imaging (MRI), were selected as magnetic core and coated with different biocompatible polymers, such as chitosan (CAN-Mag-Chitosan NPs) or polylactic co glycolic acid (PLGA) obtaining polymeric nanoparticles (CAN-Mag@PNPs), already approved for drug delivery applications. The binding efficacy of t-PA-vectorized NPs determined by exposure to different pancreatic cell lines was up to 90%, as assessed by flow cytometry. The in vivo targeting and imaging efficacy of the vectorized NPs were evaluated by applying murine pancreatic tumor models and assessed by 1.5 T magnetic resonance imaging (MRI). The t-PA-vectorized NPs as well as the protease-activated NPs with outer shell decoration (CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac) showed clearly detectable drop of subcutaneous and orthotopic tumor staining-intensity indicating a considerable uptake of the injected NPs. Post mortem NP deposition in tumors and organs was confirmed by Fe staining of histopathology tissue sections. Conclusions: The targeted NPs indicate a fast and enhanced deposition of NPs in the murine tumor models. The CAN-Mag@PNPs-PEG-REGAcp-PEG/tPA-pep1Lac interlocking steps strategy of NPs delivery and deposition in pancreatic tumor is promising
Hombres de Terranova: la pesca del bacalao 1926-2004
El hilo conductor del libro es el aspecto subjetivo, la experiencia
vivida de estos Hombres que participan en los hechos. Éste es, en definitiva,
el propósito de este trabajo: mostrar, siguiendo a Halbwachs, la existencia de
unas memorias colectivas que se entretejen con la historia general. El
comienzo de esta actividad industrial en 1926 obedece a la necesidad de
abastecer el mercado nacional de pescado seco, que en este caso es bacalao
salado. Los acontecimientos de la guerra civil española o la Segunda Guerra
Mundial, constituyen grandes hitos a tener en cuenta, ya que aportan
planificaciones económicas en los países donde se potencia una gran
concurrencia internacional, y, del mismo modo, el hecho de pasar de un
Mare Liberum, a un mar gestionado por los países ribereños, que extienden
su jurisdicción a doscientas millas marinas aguas adentro, determinará la
desaceleración de la expansión de la flota bacaladera. Se analizan
manipulaciones de conceptos y se reflexiona sobre la génesis y el desarrollo
de la sobrepesca, la situación interna de Terranova, como la emergencia de
sus propios símbolos, la llegada de la moratoria en 1992 y la no
recuperación de la especie del bacalao después de una moratoria vigente
durante más de una década
MOESM1 of Distinct pathophysiological cytokine profiles for discrimination between autoimmune pancreatitis, chronic pancreatitis, and pancreatic ductal adenocarcinoma
Additional file 1: Table S1. Comparison of cytokine levels in serum from: AIP-1, AIP-2, CP and PDAC patients