Bioorthogonal catalysis employing transition metal catalysts is a promising strategy for the in situ synthesis of imaging and therapeutic agents in biological environments. The transition metal Pd ...has been widely used as a bioorthogonal catalyst, but bare Pd poses challenges in water solubility and catalyst stability in cellular environments. In this work, Pd(0) loaded amphiphilic polymeric nanoparticles are applied to shield Pd in the presence of living cells for the in situ generation of a fluorescent dye and anticancer drugs. Pd(0) loaded polymeric nanoparticles prepared by the reduction of the corresponding Pd(II)-polymeric nanoparticles are highly active in the deprotection of pro-rhodamine dye and anticancer prodrugs, giving significant fluorescence enhancement and toxigenic effects, respectively, in HepG2 cells. In addition, we show that the microstructure of the polymeric nanoparticles for scaffolding Pd plays a critical role in tuning the catalytic efficiency, with the use of the ligand triphenylphosphine as a key factor for improving the catalyst stability in biological environments.
Display omitted
The antimicrobial action of gold depends on different factors including its oxidation state in the intra- and extracellular medium, the redox potential, its ability to produce ...reactive oxygen species (ROS), the medium components, the properties of the targeted bacteria wall, its penetration in the bacterial cytosol, the cell membrane potential, and its interaction with intracellular components. We demonstrate that different gold species are able to induce bacterial wall damage as a result of their electrostatic interaction with the cell membrane, the promotion of ROS generation, and the consequent DNA damage. In-depth genomic and proteomic studies on Escherichia coli confirmed the superior toxicity of Au (III) vs Au (I) based on the different molecular mechanisms analyzed including oxidative stress, bacterial energetic metabolism, biosynthetic processes, and cell transport. At equivalent bactericidal doses of Au (III) and Au (I) eukaryotic cells were not as affected as bacteria did, maintaining unaffected cell viability, morphology, and focal adhesions; however, increased ROS generation and disruption in the mitochondrial membrane potential were also observed. Herein, we shed light on the antimicrobial mechanisms of ionic and biogenic gold nanoparticles against bacteria. Under selected conditions antibiotic-like ionic gold can exert a strong antimicrobial activity while being harmless to human cells.
Display omitted
With a very poor prognosis and no clear etiology, glioma is the most aggressive cancer in the brain. Thanks to its versatility, nanomedicine is a promising option to overcome the ...limitations on chemotherapy imposed by the blood brain barrier (BBB). The objective of this paper was to obtain monitored tumor-targeted therapeutic nanoparticles (NPs). To that end, theranostic surfactant-coated polymer poly-Lactic-co-Glycolic Acid (PLGA) nanoplatform encapsulating doxorubicin hydrochloride (DOX) and superparamagnetic iron oxide NPs (SPIONs) were developed. Different non-ionic surfactants known as BBB crossing enhancers (Tween 80, Brij-35, Pluronic F68 or Vitamin E-TPGS) were used to develop 4 types of theranostic nanoplatforms, which were characterized in terms of size and morphology by DLS, TEM and STEM-HAADF analyses. Moreover, the 3-month stability test, the therapeutic efficacy against different glioma cell lines (U87-MG, 9L/LacZ and patient derived-neuronal stem cells) and the Magnetic Resonance Imaging (MRI) relaxivity were studied. Results showed that the synthesised nanoplatforms were stable at 4 °C after their lyophilization, being that of paramount importance to ensure a long-term stability in a future in vivo application. Furthermore, the theranostic nanoplatforms were efficient in the in vitro treatment of glioma cells, proving to have imaging efficacy as MRI contrast agents. Our results show an efficient loading of drugs and good value of the relaxivity. Therefore, the efficient theranostic hybrid nanoplatform developed here could be used to perform MRI-guided delivery of hydrophobic drugs.
Cancer is a rapidly evolving, multifactorial disease that accumulates numerous genetic and epigenetic alterations. This results in molecular and phenotypic heterogeneity within the tumor, the ...complexity of which is further amplified through specific interactions between cancer cells. We aimed to dissect the molecular mechanisms underlying the cooperation between different clones.
We produced clonal cell lines derived from the MDA-MB-231 breast cancer cell line, using the UbC-StarTrack system, which allowed tracking of multiple clones by color: GFP C3, mKO E10 and Sapphire D7. Characterization of these clones was performed by growth rate, cell metabolic activity, wound healing, invasion assays and genetic and epigenetic arrays. Tumorigenicity was tested by orthotopic and intravenous injections. Clonal cooperation was evaluated by medium complementation, co-culture and co-injection assays.
Characterization of these clones in vitro revealed clear genetic and epigenetic differences that affected growth rate, cell metabolic activity, morphology and cytokine expression among cell lines. In vivo, all clonal cell lines were able to form tumors; however, injection of an equal mix of the different clones led to tumors with very few mKO E10 cells. Additionally, the mKO E10 clonal cell line showed a significant inability to form lung metastases. These results confirm that even in stable cell lines heterogeneity is present. In vitro, the complementation of growth medium with medium or exosomes from parental or clonal cell lines increased the growth rate of the other clones. Complementation assays, co-growth and co-injection of mKO E10 and GFP C3 clonal cell lines increased the efficiency of invasion and migration.
These findings support a model where interplay between clones confers aggressiveness, and which may allow identification of the factors involved in cellular communication that could play a role in clonal cooperation and thus represent new targets for preventing tumor progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Platinum nanoparticles have been demonstrated to have excellent anticancer properties. However, because of the lack of specificity they must be delivered to the tumor in amounts sufficient to reach ...the desired therapeutic objectives. Interestingly, exosomes are considered as excellent natural selective delivery nanotools, but until know their targeting properties have not being combined with the anticancer properties of platinum nanoparticles. In this work we combine the targeting capabilities of exosomes and the antitumoral properties of ultrasmall (< 2 nm) platinum nanoparticles as a novel, low toxicity alternative to the use of cisplatin. A mild methodology based on the room temperature CO-assisted in situ reduction of Pt.sup.2+ precursor was employed to preserve the integrity of exosomes, while generating ultrasmall therapeutic PtNPs directly inside the vesicles. The resulting PtNPs-loaded exosomes constitute a novel hybrid bioartificial system that was readily internalized by the target cells inducing antiproliferative response, as shown by flow cytometry and microscopy experiments in vitro. In vivo Pt-Exos showed antitumoral properties similar to that of cisplatin but with a strongly reduced or in some cases no toxic effect, highlighting the advantages of this approach and its potential for translation to the clinic. In this study, a nanoscale vector based on ultrasmall PtNPs and exosomes has been created exhibiting antitumoral properties comparable or higher to those of the FDA approved cisplatin. The preferential uptake of PtNPs mediated by exosomal transfer between certain cell types has been exploited to create a selective antitumoral novel bioartificial system. We have demonstrated their anticancer properties both in vitro and in vivo comparing the results obtained with the administration of equivalent amounts of cisplatin, and showing a spectacular reduction of toxicity.
The supported zeolite membranes prepared in this work have been synthesised under microwave heating in order to reduce synthesis time, to prevent support dissolution, and to reproducibly obtain a ...thin defect-free zeolite layer. The MFI-type zeolite membranes were synthesised on ceramic capillaries, with a high membrane surface area-to-volume ratio (>1000
m
2
m
−3), which is by far higher than that of classical tubular supports (≪500
m
2
m
−3). The selective layer was deposited inside, outside or on both sides of the capillaries. These hydrophobic membranes were characterized and tested in pervaporation for the separation of an EtOH/H
2O: 5/95
wt.% mixture. The best results obtained at a pervaporation temperature of 45
°C, in terms of flux (1.5
kg/h
m
2) and selectivity (
α
EtOH/
H
2
O
=
54
), were achieved with the double-sided membranes.
In this work, the concept of zeolite (zeolitic) membrane is discussed from a practical perspective. We consider the limitations of the existing synthesis methods and speculate on new opportunities of ...zeolites and zeolite-type materials such as metal organic frameworks for the production of membranes. This paper focuses on the barriers that need to be eliminated before the commercialization of these membranes becomes attractive. Additional opportunities for commercialization may arise in the shape either of mixed matrix membranes, taking advantage of composites with polymers, or as zeolite coatings useful for a plethora of new applications.
A new strategy to nanoengineer multi-functional polymer-metal hybrid nanostructures is reported. By using this protocol the hurdles of most of the current developments concerning covalent and ...non-covalent attachment of polymers to preformed inorganic nanoparticles (NPs) are overcome. The strategy is based on the in situ reduction of metal precursors using the polymeric nanoparticle as a nanoreactor. Gold nanoparticles and poly(DL-lactic-co-glycolic acid), PLGA, are located in the core and shell, respectively. This novel technique enables the production of PLGA NPs smaller than 200 nm that bear either a single encapsulated Au NP or several smaller NPs with tunable sizes and a 100% loading efficiency. In situ reduction of Au ions inside the polymeric NPs was achieved on demand by using heat to activate the reductive effect of citrate ions. In addition, we show that the loading of the resulting Au NPs inside the PLGA NPs is highly dependent on the surfactant used. Electron microscopy, laser irradiation, UV-Vis and fluorescence spectroscopy characterization techniques confirm the location of Au nanoparticles. These promising results indicate that these hybrid nanomaterials could be used in theranostic applications or as contrast agents in dark-field imaging and computed tomography.
En este trabajo se analiza el alcance del principio de culpabilidad como uno de los pilares del derecho administrativo sancionador. Se abordan los supuestos en que la aplicación de este principio ...puede resultar más controvertida, como es el caso de la responsabilidad de las personas jurídicas y las infracciones de mero desconocimiento. De acuerdo con la investigación realizada, no es posible prescindir de la aplicación de este principio, más allá de que existan peculiaridades en su aplicación, entre las cuales se destaca la inversión de la carga de la prueba.
Complex nanomaterials produced by scale-up batch processes lack suitable control of shape, size distribution, chemical composition, and quality, because heat and mass transfer are seriously affected ...as the reactor volume increases. Here we use a novel continuous synthesis procedure, the active gas–liquid segmented flow, to produce noble metal-magnetic heteronanostructures with enormous interest in the fields of catalysis, biomedicine, environmental sensors, food monitoring, and chemical analysis. The microreactor technology proposed scales down the reaction volume to gain advantage of the large surface area to volume ratio with respect to conventional batch-type reactors, improving heat and mass transport and, consequently, promoting a uniform heating and mixing. The gas phase was introduced in the chemical reactor as gas slugs of nanoliter scale with a dual role: (1) passive mixing and (2) chemical directing agent to tune the crystallization of nanostructures in a continuous fashion. The shape, size, and magnetic properties of the resulting heteronanostructures, as well as the density, size, and composition of noble metal nanoparticles were tuned to show the versatility of the proposed approach in a timeline of 4 min. We demonstrated that the produced nanostructures provide excellent catalytic properties in the catalyzed hydrogenation of nitrophenols to aminophenols. Electron microscopy, UV–vis spectroscopy, and cyclic voltammetry studies showed the remarkable catalytic performance of the produced heteronanostructures.
PDF
