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Background: Alzheimer's disease (AD) has a dramatic impact on society. The therapeutic targets are located in the central nervous system (CNS), which limits the efficacy of drugs systemically administered: the blood-brain barrier (BBB) selectively allows the permeation of just a few kinds of molecules from the systemic circulation to the CNS. On the other hand, local administration routes to CNS are highly invasive., Methods: In this article, we have reviewed therapeutic approaches against AD, which are based on nanoparticles targeted to the brain and to the pathological hallmarks of the disease. The existing literature has been classified according to the AD feature that is addressed., Results: Nanoparticles have been used for the targeted delivery of drugs aiming to reduce the AD symptoms or to reverse the course of the disease. For this task the multivalency of nanoparticles has allowed their functionalization with several kinds of targeting groups, to cross the BBB and to target the place of treatment. With this approach an increased drug bioavailability has been achieved in the CNS using intravenous administration in place of more invasive administration routes. Additionally, nanoparticles have also been used in the development of vaccines and therapeutic formulations for intranasal administration., Conclusion: Targeted nanoparticles have been proved useful to enhance the performance of therapies against AD in animal models. A better understanding of AD mechanisms will help the successful application of targeted nanoparticles for combined therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Current treatment of inflammatory bowel disease is based on the use of immunosuppressants or anti-inflammatory drugs, which are characterized by important side effects that can limit their use. Previous research has been performed by administering these drugs as nanoparticles that target the ulcerated intestinal regions and increase their bioavailability. It has been reported that silk fibroin can act as a drug carrier and shows anti-inflammatory properties., Purpose: This study was designed to enhance the interaction of the silk fibroin nanoparticles (SFNs) with the injured intestinal tissue by functionalizing them with the peptide motif RGD (arginine-glycine-aspartic acid) and to evaluate the intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin nanoparticles (RGD-SFNs) in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis., Materials and Methods: SFNs were prepared by nanoprecipitation in methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as the crosslinker. The SFNs (1 mg/rat) and RGD-SFNs (1 mg/rat) were administered intrarectally to TNBS-induced colitic rats for 7 days., Results: The SFN treatments ameliorated the colonic damage, reduced neutrophil infiltration, and improved the compromised oxidative status of the colon. However, only the rats treated with RGD-SFNs showed a significant reduction in the expression of different pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and IL-12) and inducible nitric oxide synthase in comparison with the TNBS control group. Moreover, the expression of both cytokine-induced neutrophil chemoattractant-1 and monocyte chemotactic protein-1 was significantly diminished by the RGD-SFN treatment. However, both treatments improved the intestinal wall integrity by increasing the gene expression of some of its markers (trefoil factor-3 and mucins)., Conclusion: SFNs displayed intestinal anti-inflammatory properties in the TNBS model of colitis in rats, which were improved by functionalization with the RGD peptide., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis., Methods: Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically., Results: The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone., Conclusion: Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects.

For several years now, nanoscaled materials have been implemented in biotechnological applications related to animal (in particular human) cells and related pathologies. However, the use of nanomaterials in plant biology is far less widespread, although their application in this field could lead to the future development of plant biotechnology applications. For any practical use, it is crucial to elucidate the relationship between the nanomaterials and the target cells. In this work we have evaluated the behavior of two types of nanomaterials, quantum dots and superparamagnetic nanoparticles, on Fusarium oxysporum, a fungal species that infects an enormous range of crops causing important economic losses and is also an opportunistic human pathogen. Our results indicated that both nanomaterials rapidly interacted with the fungal hypha labeling the presence of the pathogenic fungus, although they showed differential behavior with respect to internalization. Thus, whereas magnetic nanoparticles appeared to be on the cell surface, quantum dots were significantly taken up by the fungal hyphae showing their potential for the development of novel control approaches of F. oxysporum and related pathogenic fungi following appropriate functionalization. In addition, the fungal germination and growth, accumulation of ROS, indicative of cell stress, and fungal viability have been evaluated at different nanomaterial concentrations showing the low toxicity of both types of nanomaterials to the fungus. This work represents the first study on the behavior of quantum dots and superparamagnetic particles on fungal cells, and constitutes the first and essential step to address the feasibility of new nanotechnology-based systems for early detection and eventual control of pathogenic fungi.

Bacterial resistance to antibiotics is widely regarded as a major public health concern with last resort MRSA treatments like vancomycin now encountering resistant strains. TFDs (Transcription Factor Decoys) are oligonucleotide copies of the DNA-binding sites for transcription factors. They bind to and sequester the targeted transcription factor, thus inhibiting transcription of many genes. By developing TFDs with sequences aimed at inhibiting transcription factors controlling the expression of highly conserved bacterial cell wall proteins, TFDs present as a potential method for inhibiting microbial growth without encountering typical resistance mechanisms. However, the efficient protection and delivery of the TFDs inside the bacterial cells is a critical step for the success of this technology. Therefore, in our study, specific TFDs against S. aureus were complexed with two different types of nanocarriers: cationic nanostructured lipid carriers (cNLCs) and chitosan-based nanoparticles (CS-NCs). These TFD-carrier nanocomplexes were characterized for size, zeta potential and TFD complexation or loading efficiency in a variety of buffers. In vitro activity of the nanocomplexes was examined alone and in combination with vancomycin, first in methicillin susceptible strains of S. aureus with the lead candidate advancing to tests against MRSA cultures. Results found that both cNLCs and chitosan-based carriers were adept at complexing and protecting TFDs in a range of physiological and microbiological buffers up to 72 hours. From initial testing, chitosan-TFD particles demonstrated no visible improvements in effect when co-administered with vancomycin. However, co-delivery of cNLC-TFD with vancomycin reduced the MIC of vancomycin by over 50% in MSSA and resulted in significant decreases in viability compared with vancomycin alone in MRSA cultures. Furthermore, these TFD-loaded particles demonstrated very low levels of cytotoxicity and haemolysis in vitro. To our knowledge, this is the first attempt at a combined antibiotic/oligonucleotide-TFD approach to combatting MRSA and, as such, highlights a new avenue of MRSA treatment combining traditional small molecules drugs and bacterial gene inhibition. [ABSTRACT FROM AUTHOR]

Magnesium oxide nanoparticles (MgO NPs) have attracted considerable interest as antimicrobial agents in a wide variety of applications. We report a simple synthetic route towards MgO NPs (average diameter 10 nm) possessing potent antibacterial activity against both Gram-negative and Gram-positive bacteria. Detailed electron microscopy studies show how these particles induce oxidative stress, cell membrane leakage and cell death in bacteria at low NP concentrations, but remain non-toxic to eukaryotic cells. Applying a homogeneous dispersion of these nanoparticles on 18th century paper proved to be a highly effective means of preventing bacterial colonisation without altering the appearance of the paper samples, thus opening the doors to the use of these colourless, low-cost, and scalable nanoparticles for preventing biodeterioration in a range of paper-based objects and surfaces. • Nano-magnesium oxide particles (MgO NPs) of average size of around 10 nm have been synthesised using a simple one-pot synthesis. • The MgO NPs offer potent bactericidal activity but are non-toxic to mammalian cells at the same concentrations. • A combination of electron microscopy techniques shows how these nanoparticles produce oxidative stress, followed by cell membrane leakage and death. • The MgO NPs prevented bacterial colonisation of 18th century papers from the Archives of the Spanish Royal Botanic Garden. [ABSTRACT FROM AUTHOR]

Superparamagnetic magnetite nanoparticles coated withan ultrathin(∼1 nm) magnesium oxide (MgO) layer have been synthesized bycombining coprecipitation and sol–gel methods. A thorough chemicaland structural characterization has been carried out by means of highresolution transmission electron microscopy (HRTEM), X-ray diffraction(XRD), X-ray energy dispersive spectroscopy (EDS), dynamic light scattering(DLS), and thermogravimetric analysis (TGA). Aberration correctedHRTEM experiments with subangstrom spatial resolution have allowedus to distinguish the ultrathin MgO shell that grows epitaxially onthe magnetic cores. The capability of the MgO shell to protect themagnetic nuclei from oxidation up to 600 °C has been demonstrated.The magnetic properties of the material have been studied before andafter the coating procedure. The superparamagnetism of the magnetitenuclei at room temperature is preserved even after calcination. Thepossibility of obtaining particles of controlled size coated withan isolating layer of nanometric thickness and high thermal stabilitymakes the combination of the two synthesis methods used in this worka starting procedure to obtain nanometric powders suitable for technologicalapplications, such as high-frequency electronics. These particles,after the appropriated functionalization, are also potential candidatesto be used in biomedical applications. [ABSTRACT FROM AUTHOR]

Enzyme immobilization on magnetic supports represents a great advantage for the industrial application of enzymatic catalysis since it allows an easy recovery of the catalyst, avoiding any contamination of the product by residual enzyme. Iron oxide nanoparticles are very useful for this purpose. Using a polymer to diminish the interaction between the magnetic cores themselves, can improve the colloidal stability of the support and prevent any interaction with the environment that would affect both support properties and enzyme stability. For this reason, in this work different magnetic micro-supports, based on polydopamine-coated iron oxide nanoparticles with a multi polysaccharide shell, have been developed. These supports have been used to immobilize chloroperoxidase, a very interesting enzyme, able to catalyze many reactions of large-scale interest, but whose application is limited by its sensitivity to reaction conditions. The multi polysaccharide shells of the supports were obtained through a combination of chitosan and alginate. An in-depth analysis of physicochemical and catalytic properties of all the developed magnetic supports is reported. CPO was successfully immobilized with an efficiency of entrapment between 92% and 100% in the case of supports with chitosan in the interior or outer shell respectively. A very good chemical stability of the support under reaction conditions was observed in the case of an interior shell of alginate and an outer coating of chitosan, together with an excellent reusability of the immobilized enzyme, that was recycled to catalyze up to 25 consecutive reaction cycles. [ABSTRACT FROM AUTHOR]