Decoration of nanovesicles with pH (low) insertion peptide (pHLIP) for targeted delivery

Acidity at surface of cancer cells is a hallmark of tumor microenvironments, which does not depend on tumor perfusion, thus it may serve as a general biomarker for targeting tumor cells. We used the pH (low) insertion peptide (pHLIP) for decoration of liposomes and niosomes. pHLIP senses pH at the surface of cancer cells and inserts into the membrane of targeted cells, and brings nanomaterial to close proximity of cellular membrane. DMPC liposomes and Tween 20 or Span 20 niosomes with and without pHLIP in their coating were fully characterized in order to obtain fundamental understanding on nanocarrier features and facilitate the rational design of acidity sensitive nanovectors. The samples stability over time and in presence of serum was demonstrated. The size, ζ-potential, and morphology of nanovectors, as well as their ability to entrap a hydrophilic probe and modulate its release were investigated. pHLIP decorated vesicles could be useful to obtain a prolonged (modified) release of biological active substances for targeting tumors and other acidic diseased tissues

Smart magnetic nanovesicles for theranostic application: Preparation and characterization

Nanomedicines are submicrometer-sized carrier materials designed to improve the biodistribution of systemically administered (chemo)therapeutic agents. By delivering pharmacologically active agents more effectively and more selectively to the pathological site nanomedicines aim to improve the balance between the efficacy and the toxicity of systemic (chemo)therapeutic administrations. Nanomedicine formulations have also been used for imaging applications and, in recent years, for theranostic approaches, that is, for systems and strategies in which disease diagnosis and therapy are combined. On the one hand, “classical” drug delivery systems are being co-loaded with both drugs and contrast agents. Actually, nanomaterials with an intrinsic ability to be used for imaging purposes, such as iron-oxide–based magnetic nanoparticles (MNPs), are increasingly being loaded with drugs or alone for combining disease diagnosis and therapy. In this study, non-ionic surfactant vesicles loaded with lipophilic and hydrophilic MNPs have been prepared. Vesicles have been characterized in terms of dimensions, ζ-potential, time stability, bilayer characteristics and overall iron content. The encouraging obtained results confirm that Tween 20 and Span 20 vesicles could be promising carriers for the delivery of hydrophilic and lipophilic MNPs, respectively, thereby prompting various opportunities for the development of suitable theranostic strategies. The analyzed formulations confirm the importance of surfactant chemical-physical characteristics in entrapping the MNPs of different polarity, highlighting the high versatility of niosomal bilayer and structure; property that make them so appealing among drug delivery nanocarriers

Static stress drop as determined from geodetic strain rates and statistical seismicity

Two critical items in the energetic budget of a seismic province are the strain rate, which is measured geodetically on the Earth’s surface, and the yearly number of earthquakes exceeding a given magnitude. Our study is based on one of the most complete and recent seismic catalogs of Italian earthquakes and on the strain rate map implied by a multi-year velocity solution for permanent GPS stations. For 36 homogeneous seismic zones, we used the appropriate Gutenberg Richter relation based on the seismicity catalog to estimate a seismic strain rate, which is the strain rate associated with the mechanical work due to a co-seismic displacement. The volume storing most of the elastic energy is associated with the long-term deformation of each seismic zone, and therefore, the seismic strain rate is inversely proportional to the static stress drop. The GPS-derived strain rate for each seismic zone limits the corresponding seismic strain rate, and an upper bound for the average stress drop is estimated. These results demonstrated that the implied regional static stress drop ranged from 0.1 to 5.7 MPa for catalog earthquakes in the moment magnitude range [4.5–7.3]. These results for stress drop are independent of the “a” and “b” regional parameters and heat flow but are very sensitive to the assumed maximum magnitude of a seismic province. The data do not rule out the hypothesis that the stress drop positively correlates with the time elapsed after the largest earthquake recorded in each seismic zone

Current trends in ATRA delivery for cancer therapy

All-Trans Retinoic Acid (ATRA) is the most active metabolite of vitamin A. It is critically involved in the regulation of multiple processes, such as cell differentiation and apoptosis, by activating specific genomic pathways or by influencing key signaling proteins. Furthermore, mounting evidence highlights the anti-tumor activity of this compound. Notably, oral administration of ATRA is the first choice treatment in Acute Promyelocytic Leukemia (APL) in adults and NeuroBlastoma (NB) in children. Regrettably, the promising results obtained for these diseases have not been translated yet into the clinics for solid tumors. This is mainly due to ATRA-resistance developed by cancer cells and to ineffective delivery and targeting. This up-to-date review deals with recent studies on different ATRA-loaded Drug Delivery Systems (DDSs) development and application on several tumor models. Moreover, patents, pre-clinical, and clinical studies are also reviewed. To sum up, the main aim of this in-depth review is to provide a detailed overview of the several attempts which have been made in the recent years to ameliorate ATRA delivery and targeting in cancer

Angiosarcoma of the breast: a new therapeutic approach?

Introduction Angiosarcomas are highly malignant endothelial cell tumors with poor prognosis. These can be due to breast cancer itself or to subsequent therapeutic modalities. No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Presentation of the case We report the case of a 76-year-old woman who developed an exuberant and aggressive post radiation angiosarcoma of the breast and discuss different aspects of therapy for this disease. A total left mastectomy was performed, followed by a right mastectomy. The lesions into the chest wall, and multiple abdominal skin nodules were treated with local Electrochemotherapy (ECT) with intravenous bleomicin. Discussion No evidence-based guidelines exist concerning the ideal treatment of angiosarcomas. Electrochemotherapy (ECT) is an efficient palliative treatment of cutaneous and subcutaneous tumor nodules. It consists of the combination of a cytotoxic drug and electroporation, using appropriate electrical parameters; destabilization of the membrane is reversible, ensuring a high survival of permeabilized cells and the delivery of non-permeant molecules inside the cell. Conclusion Due to the rarity of the disease, prospective studies concerning adjuvant or neoadjuvant therapy are limited and no evidence-based guidelines exist. The response to chemotherapy seems to be poor. Treatment with ECT in addition to systemic chemotherapy achieves a complete response in all the lesions and improving patient body image perception

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention

Interseismic ground velocities in Central Apennines from GPS and InSAR measurements: new contributions for seismic hazard models by preliminary results of ESA CHARMING project

The contribution of space geodetic techniques to interseismic velocity estimation, and thus seismic hazard modelling, has been recognized since two decades and made possible in more recent years by the increased availability and accuracy of geodetic measurements. We present the preliminary results of a feasibility study performed within the CHARMING project (Constraining Seismic Hazard Models with InSAR and GPS), funded by the European Space Agency (ESA). For a 200 km x 200 km study area, covering the Abruzzi region (central Italy) we measure the mean surface deformation rates from Synthetic Aperture Radar and GPS, finding several local to regional deformation gradients consistent with the tectonic context. We then use a kinematic finite element model to derive the long-term strain rates, as well as earthquake recurrence relations. In turn these are input to state-of-the-art probabilistic seismic hazard models, the output of which is validated statistically using data from the Italian national accelerometric and macroseismic intensity databases.Published373-3773T. Pericolosità sismica e contributo alla definizione del rischioN/A or not JCRope

Antimicrobial essential oil formulation: chitosan coated nanoemulsions for nose to brain delivery

Brain infections as meningitis and encephalitis are attracting a great interest. Challenges in the treatment of these diseases are mainly represented by the blood brain barrier (BBB) that impairs the efficient delivery of even very potent drugs to reach the brain. The nose to the brain administration route, is a non-invasive alternative for a quick onset of action, and enables the transport of numerous medicinal agents straight to the brain thus workarounding the BBB through the highly vascularized olfactory region. In this report, Thymus vulgaris and Syzygium aromaticum essential oils (EOs) were selected to be included in chitosan coated nanoemulsions (NEs). The EOs were firstly analyzed to determine their chemical composition, then used to prepare NEs, that were deeply characterized in order to evaluate their use in intranasal administration. An in vitro evaluation against a collection of clinical isolated bacterial strains was carried out for both free and nanoemulsioned EOs. Chitosan coated NEs showed to be a potential and effective intranasal formulation against multi-drug resistant Gram-negative bacteria such as methicillin-susceptible Staphylococcus aureus and multi-drug resistant Gram-negative microorganisms including carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae

Mid-term review results of the ESA STSE Pathfinder CHARMING project (Constraining Seismic Hazard Models with InSAR and GPS)

We probe the feasibility of integrating GPS and Synthetic Aperture Radar deformation rates within the seismic hazard models of the central Apennines (Italy), exploiting data from over 100 GPS stations and the ~20- year long ERS and ENVISAT SAR image archive. We then use a kinematic finite element model to derive the long-term strain rates, as well as earthquake recurrence relations. In turn these are input to state-of-the-art probabilistic seismic hazard models, the output of which is validated statistically using data from the Italian national accelerometric and macroseismic intensity databases.Published23-273T. Pericolosità sismica e contributo alla definizione del rischioN/A or not JCRrestricte

Nanoemulsions of Satureja montana essential oil. Antimicrobial and antibiofilm activity against avian Escherichia coli strains

Satureja montana essential oil (SEO) presents a wide range of biological activities due to its high content of active phytochemicals. In order to improve the essential oil’s (EO) properties, oil in water nanoemulsions (NEs) composed of SEO and Tween-80 were prepared, characterized, and their antimicrobial and antibiofilm properties assayed against Escherichia coli strains isolated from healthy chicken. Since surfactant and oil composition can strongly influence NE features and their application field, a ternary phase diagram was constructed and evaluated to select a suitable sur-factant/oil/water ratio. Minimal inhibitory concentration and minimal bactericidal concentration of NEs, evaluated by the microdilution method, showed that the SEO NE formulation exhibited higher inhibitory effects against planktonic E. coli than SEO alone. The quantification of biofilm production in the presence of NEs, assessed by crystal violet staining and scanning electron microscopy, evi-denced that sub-MIC concentrations of SEO NEs enable an efficient reduction of biofilm production by the strong producer strains. The optimized nanoemulsion formulation could ensure food safety quality, and counteract the antibiotic resistance of poultry associated E. coli, if applied/aerosolized in poultry farms