Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein

Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro validation of a synthetic mimic of Smac/DIABLO, based on fluorescent polyethylene glycol (PEG)-coated silica-core nanoparticles (NPs) carrying a Smac/DIABLO-derived pro-apoptotic peptide and a tumor-homing integrin peptide ligand. At low \u3bcM concentration, the NPs showed significant toxicity towards A549, U373, and HeLa cancer cells and modest toxicity towards other integrin-expressing cells, correlated with integrin-mediated cell uptake and consequent highly increased levels of apoptotic activity, without perturbing cells not expressing the \u3b15 integrin subunit

Responsive Nucleic Acid-Based Organosilica Nanoparticles

The development of smart nanoparticles (NPs) that encode responsive features in the structural framework promises to extend the applications of NP-based drugs, vaccines, and diagnostic tools. New nanocarriers would ideally consist of a minimal number of biocompatible components and exhibit multiresponsive behavior to specific biomolecules, but progress is limited by the difficulty of synthesizing suitable building blocks. Through a nature-inspired approach that combines the programmability of nucleic acid interactions and sol-gel chemistry, we report the incorporation of synthetic nucleic acids and analogs, as constitutive components, into organosilica NPs. We prepared different nanomaterials containing single-stranded nucleic acids that are covalently embedded in the silica network. Through the incorporation of functional nucleic acids into the organosilica framework, the particles respond to various biological, physical, and chemical inputs, resulting in detectable physicochemical changes. The one-step bottom-up approach used to prepare organosilica NPs provides multifunctional systems that combine the tunability of oligonucleotides with the stiffness, low cost, and biocompatibility of silica for different applications ranging from drug delivery to sensing

Supramolecular Nucleic Acid-Based Organosilica Nanoparticles Responsive to Physical and Biological Inputs

Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics

Assessing the costs of protection in a context of switching stochastic regimes

We consider the problem of cost assessment in the context of switching stochastic regimes. The dynamics of a given asset include a background noise, described by a Brownian motion and a random shock, the impact of which is characterized by changes in the coefficient diffusions. A particular economic agent that is directly exposed to variations in the underlying asset price, incurs some costs, , when the underlying asset price reaches a certain threshold, L. Ideally, the agent would make advance provision, or hedge, for these costs at time 0. We evaluate the amount of provision, or the hedging premium, , for these costs in the disrupted environment, with changes in the regime for a given time horizon, and analyse the sensitivity of this amount to possible model misspecifications

Dataset - Gendered Attitudes

Data used to investigate the role of sexism as a determinant of the vote in the 2016 US presidential election. The file includes data for proxies of sexists atitudes towards women, elaborated with Google query data and survey-based data, and data for other variables that are known to determine vote, such as home state, unemployment rates and demographic variables, all at media market level

Dataset - Gendered Attitudes

Data used to investigate the role of sexism as a determinant of the vote in the 2016 US presidential election. The file includes data for proxies of sexists atitudes towards women, elaborated with Google query data and survey-based data, and data for other variables that are known to determine vote, such as home state, unemployment rates and demographic variables, all at media market level.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Dataset - Gendered Attitudes

Data used to investigate the role of sexism as a determinant of the vote in the 2016 US presidential election. The file includes data for proxies of sexists atitudes towards women, elaborated with Google query data and survey-based data, and data for other variables that are known to determine vote, such as home state, unemployment rates and demographic variables, all at media market level.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Highly degradable imine-doped mesoporous silica particles

The degradation of mesoporous silica particles (MSPs) in water is a key aspect that boosts their use especially in bio-related fields. Although MSP degradation in aqueous media has been proven, big efforts have been devoted to tuning silica dissolution in order to obtain functional materials whose degradation can be finely controlled and enhanced, to tackle the issue of bioaccumulation. In particular, the introduction of stimuli-responsive functional groups into the silica framework was proven to be a successful strategy. Yet, the fast dissolution of silica particles in aqueous media in the absence of external stimuli has to be fully addressed. In this context, we reported herein the preparation and thorough characterisation of MSPs containing imine groups embedded within the silica framework (Im-MSPs). Particles with different contents of imine groups have been investigated in order to assess the effect on the physicochemical properties and the Im-MSPs showed fast degradation in both acidic and neutral aqueous solutions, at a rate that depended on the pH value. Of special interest is their fast degradation at acidic pH, where instead MSPs are normally more stable. The described results unveil the potential of these particles in applications that require a fast degradation in aqueous media