An integrated approach for the systematic evaluation of polymeric nanoparticles in healthy and diseased organisms

Innovative strategies that utilize nanoparticles (NPs) for a better delivery of drugs and to improve their therapeutic efficacy have been widely studied in many clinical fields, including oncology. To develop safe and reliable devices able to reach their therapeutic target, a hierarchical characterization of NP interactions with biological fluids, cells, and whole organisms is fundamental. Unfortunately, this aspect is often neglected and the development of standardized characterization methods would be of fundamental help to better elucidate the potentials of nanomaterials, even before the loading of the drugs. Here, we propose a multimodal in vitro/in vivo/ex vivo platform aimed at evaluating these interactions for the selection of the most promising NPs among a wide series of materials. To set the system, we used non-degradable fluorescent poly(methyl-methacrylate) NPs of different sizes (50, 100, and 200 nm) and surface charges (positive and negative). First we studied NP stability in biological fluids. Then, we evaluated NP interaction with two cell lines of triple-negative breast cancer (TNBC), 4T1, and MDA-MB231.1833, respectively. We found that NPs internalize in TNBC cells depending on their physico-chemical properties without toxic effects. Finally, we studied NP biodistribution in terms of tissue migration and progressive clearance in breast-cancer bearing mice. The use of highly stable poly(methyl-methacrylate) NPs enabled us to track them for a long time in cells and animals. The application of this platform to other nanomaterials could provide innovative suggestions for the development of a systematic method of characterization to select the most reliable nanodrug candidates for biomedical applications.     

Tuning in-meso-crystallized lysozyme polymorphism by lyotropic liquid crystal symmetry

Lipid-based lyotropic liquid crystals (LLCs) show great potential for applications in fields as diverse as food technology, cosmetics, pharmaceutics, or structural biology. Recently, these systems have provided a viable alternative to the difficult process of membrane protein crystallization, owing to their similarities with cell membranes. Nonetheless, the process of in-meso crystallization of proteins still remains poorly understood. In this study, we demonstrate that in-meso crystal morphologies of lysozyme (LSZ), a model hydrophilic protein, can be controlled by both the composition and symmetry of the mesophase, inferring a possible general influence of the LLC space group on the protein crystal polymorphism. Lysozyme was crystallized in-meso from three common LLC phases (lamellar, inverse hexagonal, and inverse bicontinuous cubic) composed of monolinolein and water. Different mixing ratios of mesophase to crystallization buffer were used in order to tune crystallization both in the bulk mesophase and in excess water conditions. Two distinct mechanisms of crystallization were shown to take place depending on available water in the mesophases. In the bulk mesophases, protein nuclei form and grow within structural defects of the mesophase and partially dehydrate the system inducing order-to-order transitions of the liquid crystalline phase toward stable symmetries in conditions of lower hydration. The formed protein crystals eventually macrophase separate from the mesophase allowing the system to reach its final symmetry. On the other hand, when excess water is available, protein molecules diffuse from the water channels into the excess water, where the crystallization process can take place freely, and with little to no effect on the structure and symmetry of the lyotropic liquid crystals.     

Ionic strength effects on the critical micellar concentration of ionic and nonionic surfactants: the binding model

We have recently investigated the aggregation behavior of zwitterionic n-dodecyl phosphocholine in the presence of high salt. As double logarithmic Corrin-Harkins plots of the critical micellar concentration versus the salt concentration were not linear, here we re-examine those data in the context of the binding model of surfactant aggregation, as previously developed by us for ionic surfactants. We have also re-examined plenty of data available in the literature on the salt-dependent aggregation of neutral surfactants. The use of double-logarithmic plots allowed us to show that the binding model is of general applicability. Indeed, it permits unified treatment of ionic and uncharged aggregation without requiring the introduction of linear terms in the salt concentration, as needed in the empirical Corrin-Harkins treatment of nonionic surfactants. The use of this model could be of help in a broad range of surfactant-based applications in the presence of high salt.     

Self-rewetting carbon nanofluid as working fluid for space and terrestrial heat pipes

Thermal management is very important in modern electronic systems. Recent researches have been dedicated to the study of the heat transfer performances of binary heat transfer fluids with peculiar surface tension properties and in particular to that of “self-rewetting fluids”, i.e., liquids with a surface tension increasing with temperature and concentration. Since in the course of liquid/vapor-phase change, self-rewetting fluids behavior induces a rather strong liquid inflow (caused by both temperature and concentration gradients) from the cold region (where liquid condensates) to the hot evaporator region, this fluids have been proposed and investigated as new heat transfer fluids for advanced heat transfer devices, e.g., heat pipes or heat spreaders for terrestrial and space applications (Savino et al. in Space Technol 25(1):59–61, 2009). The present work is dedicated to the study of the thermophysical properties of a new class of heat transfer fluids based on water/alcohol solutions with suspended carbon nanostructures, in particular single-wall carbon nanohorns (SWNH), synthesized by a homemade apparatus with an AC arc discharge in open air (Mirabile Gattia et al. in Nanotechnology 18:255604, 2007). SWNHs are cone-shaped nanoparticles with diameters between 1 and 5 nm and lengths in the range of 20–100 nm. SWNHs could be found in the form of quite-spherical aggregates with diameters ranging from 20 to 100 nm. The paper also discusses the results of these investigations and laboratory characterization tests of different heat pipes, including reference ordinary heat pipes and innovative pipes filled with self-rewetting fluids and self-rewetting nanofluids. The potential interest of the proposed studies stems from the large number of possible industrial applications, including space technologies and terrestrial applications, such as cooling of electronic components.     

Effective Critical Micellar Concentration of a Zwitterionic Detergent: A Fluorimetric Study on <Emphasis Type="BoldItalic">n</Emphasis>-Dodecyl Phosphocholine

We have investigated the effect of ionic strength on the aggregation behavior of n-dodecyl phosphocholine. On the basis of the classical Corrin–Harkins relation, the critical micellar concentration of this detergent decreases with a biphasic trend on lithium chloride addition. It is nearly constant below 150 mM salt, with a mean value of 0.91 mM, whereas it undergoes a dramatic 80-fold decrease in 7 M LiCl. Such a drop in the critical micellar concentration could be explained by the effect of salting out and the implication of phosphocholine head groups on the organization of surrounding water. Knowledge of the effective critical micellar concentration of n-dodecyl phosphocholine could be useful in the purification of membrane proteins in non-denaturing conditions.     

Singular Hartree equation in fractional perturbed Sobolev spaces

We establish the local and global theory for the Cauchy problem of the singular Hartree equation in three dimensions, that is, the modification of the non-linear Schrödinger equation with Hartree non-linearity, where the linear part is now given by the Hamiltonian of point interaction. The latter is a singular, self-adjoint perturbation of the free Laplacian, modelling a contact interaction at a fixed point. The resulting non-linear equation is the typical effective equation for the dynamics of condensed Bose gases with fixed point-like impurities. We control the local solution theory in the perturbed Sobolev spaces of fractional order between the mass space and the operator domain. We then control the global solution theory both in the mass and in the energy space.     

The Potential of a Protein Model Synthesized Absent of Methionine

Methionine is an amino acid long thought to be essential, but only in the case of protein synthesis initiation. In more recent years, methionine has been found to play an important role in antioxidant defense, stability, and modulation of cell and protein activity. Though these findings have expanded the previously held sentiment of methionine having a singular purpose within cells and proteins, the essential nature of methionine can still be challenged. Many of the features that give methionine its newfound functions are shared by the other sulfur-containing amino acid: cysteine. While the antioxidant, stabilizing, and cell/protein modulatory functions of cysteine have already been well established, recent findings have shown a similar hydrophobicity to methionine which suggests cysteine may be able to replace methionine in all functions outside of protein synthesis initiation with little effect on cell and protein function. Furthermore, a number of novel mechanisms for alternative initiation of protein synthesis have been identified that suggest a potential to bypass the traditional methionine-dependent initiation during times of stress. In this review, these findings are discussed with a number of examples that demonstrate a potential model for synthesizing a protein in the absence of methionine.     

Chemically induced phase separated morphologies in epoxy resin‐hyperbranched polymer blends

The morphology build‐up in toughened epoxy blends using reactive hyperbranched dendritic polymers (HBP) and amine‐cured epoxy resins has been investigated in the present work. By changing the processing conditions or the surface chemistry of the modifier, very different morphologies can be obtained, ranging from homogeneous blends to coarse two‐phase systems. The morphology characterised by electron and optical microscopy has been interpreted combining constitutive equations for phase separation and thermodynamic modelling of phase interactions. The latter model, based on the Flory‐Huggins lattice theory, was modified in order to take into account the addition reactivity of the HBP modifiers. This approach proved successful and can be used as a tool for final morphology prediction in any reactive blend formulation.