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.     

Information theory applied to econophysics: stock market behaviors

The use of data compressor techniques has allowed to recognize magnetic transitions and their associated critical temperatures [E.E. Vogel, G. Saravia, V. Cortez, Physica A 391, 1591 (2012)]. In the present paper we introduce some new concepts associated to data recognition and extend the use of these techniques to econophysics to explore the variations of stock market indicators showing that information theory can help to recognize different regimes. Modifications and further developments to previously introduced data compressor wlzip are introduced yielding two measurements. Additionally, we introduce an algorithm that allows to tune the number of significant digits over which the data compression is due to act complementing, this with an appropriate method to round off the truncation. The application is done to IPSA, the main indicator of the Chilean Stock Market during the year 2010 due to availability of quality data and also to consider a rare effect: the earthquake of the 27th of February on that year which is as of now the sixth strongest earthquake ever recorded by instruments (8.8 Richter scale) according to United States Geological Survey. Along the year 2010 different regimes are recognized. Calm days show larger compression than agitated days allowing for classification and recognition. Then the focus turns onto selected days showing that it is possible to recognize different regimes with the data of the last hour (60 entries) allowing to determine actions in a safer way. The “day of the week” effect is weakly present but “the hour of the day” effect is clearly present; its causes and implications are discussed. This effect also establishes the influence of Asian, European and American stock markets over the smaller Chilean Stock Market. Then dynamical studies are conducted intended to search a system that can help to realize in real time about sudden variations of the market; it is found that information theory can be really helpful in this respect.     

Sulfides: chemical ionization induced fragmentation studied with Proton Transfer Reaction‐Mass Spectrometry and density functional calculations

We report the energy‐dependent fragmentation patterns upon protonation of eight sulfides (organosulfur compounds) in Proton Transfer Reaction‐Mass Spectrometry (PTR‐MS). Studies were carried out, both, experimentally with PTR‐MS, and with theoretical quantum‐chemical methods. Charge retention usually occurred at the sulfur‐containing fragment for short chain sulfides. An exception to this is found in the unsaturated monosulfide allylmethyl sulfide (AMS), which preferentially fragmented to a carbo‐cation at m/z 41, C₃H₅⁺. Quantum chemical calculations (DFT with the M062X functional 6‐31G(d,p) basis sets) for the fragmentation reaction pathways of AMS indicated that the most stable protonated AMS cation at m/z 89 is a protonated (cyclic) thiirane, and that the fragmentation reaction pathways of AMS in the drift tube are kinetically controlled. The protonated parent ion MH⁺ is the predominant product in PTR‐MS, except for diethyl disulfide at high collisional energies. The saturated monosulfides R‐S‐R’ (with R<R’) have little or no fragmentation, at the same time the most abundant fragment ion is the smaller R‐S⁺ fragment. The saturated disulfides R‐S‐S‐R display more fragmentation than the saturated monosulfides, the most common fragments are disulfide containing fragments or long‐chain carbo‐cations. The results rationalize fragmentation data for saturated monosulfides and disulfides and represent a detailed analysis of the fragmentation of an unsaturated sulfide. Apart from the theoretical interest, the results are in support of the quantitative analysis of sulfides with PTR‐MS, all the more so as PTR‐MS is one of a few techniques that allow for ultra‐low quantitative analysis of sulfides. Copyright © 2013 John Wiley & Sons, Ltd.     

Tailored vapor-phase growth of Cu(x)O-TiO2 (x = 1, 2) nanomaterials decorated with Au particles

We report on the fabrication of Cu(x)O-TiO(2) (x = 1, 2) nanomaterials by an unprecedented vapor-phase approach. The adopted strategy involves the growth of porous Cu(x)O matrices by means of chemical vapor deposition (CVD), followed by the controlled dispersion of TiO(2) nanoparticles. The syntheses are performed on Si(100) substrates at temperatures of 400-550 °C under wet oxygen atmospheres, adopting Cu(hfa)(2)·TMEDA (hfa = 1,1,1,5,5,5-hexafluoro-2,4-pentanedionate; TMEDA = N,N,N',N'-tetramethylethylenediamine) and Ti(O-(i)Pr)(2)(dpm)(2) (O-(i)Pr = isopropoxy; dpm = 2,2,6,6-tetramethyl-3,5-heptanedionate) as copper and titanium precursors, respectively. Subsequently, finely dispersed gold nanoparticles are introduced in the as-prepared systems via radio frequency (RF)-sputtering under mild conditions. The synthesis process results in the formation of systems with chemical composition and nano-organization strongly dependent on the nature of the initial Cu(x)O matrix and on the deposited TiO(2) amount. The decoration with low-size gold clusters paves the way to the engineering of hierarchically organized nanomaterials.     

Metabolite profiling on apple volatile content based on solid phase microextraction and gas-chromatography time of flight mass spectrometry

A headspace SPME GC-TOF-MS method was developed for the acquisition of metabolite profiles of apple volatiles. As a first step, an experimental design was applied to find out the most appropriate conditions for the extraction of apple volatile compounds by SPME. The selected SPME method was applied in profiling of four different apple varieties by GC-EI-TOF-MS. Full scan GC-MS data were processed by MarkerLynx software for peak picking, normalisation, alignment and feature extraction. Advanced chemometric/statistical techniques (PCA and PLS-DA) were used to explore data and extract useful information. Characteristic markers of each variety were successively identified using the NIST library thus providing useful information for variety classification. The developed HS-SPME sampling method is fully automated and proved useful in obtaining the fingerprint of the volatile content of the fruit. The described analytical protocol can aid in further studies of the apple metabolome.     

Miniaturized bending-free solitons by restoring symmetry in periodically biased photorefractives

We consider optical propagation through a centrosymmetric photorefractive crystal with the externally applied bias voltage modulated along the optical propagation direction. We analytically prove that, if the modulation scale is smaller than the optical diffraction length, the resulting effective nonlinearity has an even parity in the transverse plane for an even-symmetric intensity profile and supports bending-free solitons down to few-micrometer beam widths. Numerical integration of the full photorefractive model for light-matter interaction allows us to confirm the feasibility of these miniaturized solitons and, for longer modulation periods, to investigate the excitation of self-trapped wiggling optical beams.     

Ionic liquids screening for desulfurization of natural gasoline by liquid–liquid extraction

Seventy five ionic liquids (ILs) were tested as a sequestering agent of sulfured compounds in natural gasoline (NG). Desulphurization of NG was performed by means of liquid–liquid extraction method at room temperature and atmospheric pressure. Experimental ILs containing imidazolium, pyridinium, and ammonium cations along with organic and inorganic anions were synthesized conventionally and under microwave and sonochemical conditions. The effect of the molecular structure of ILs on the desulfurization efficiency of NG with high sulfur content was evaluated. Analysis indicated that the anion type played a more important role than the cation on the desulphurization process. ILs based on halogen–ferrates and halogen–aluminates exhibited the highest efficiency in sulfur removal, and their efficiency is further improved when there is an excess of metallic salt in a ratio of at least 1:1.3 during the synthesis of the corresponding IL. An explanation for the ability of metallic ILs to remove sulfur-containing compounds from natural gasoline based on the ratio of the ionic charge to the atomic radius is proposed. Furthermore, a method to recover and reuse water-sensitive to halogenated precursors is described.     

A further investigation about a simple model of the hunting behavior of some old locomotives

This study is concerned with forced damped purely nonlinear oscillators and their behaviour at different excitation frequencies. First, their dynamics is considered numerically for the response determined in the vicinity of a backbone curve with the aim of detecting coexisting responses that have not been found analytically so far. Both the cases of low and high excitation amplitudes are investigated. Second, the angular excitation frequency is lowered significantly for different powers of nonlinearity, and the system’s behaviour is examined qualitatively, which has not been considered previously related to a general class of purely nonlinear oscillators. It is illustrated that the response at a low-valued angular excitation frequency has a form of bursting oscillations, consisting of fast oscillations around a slow flow. Finally, approximate analytical solutions are presented for the slow and fast flow for a general class of purely nonlinear oscillators.     

Reversible tuning of luminescence and magnetism in a structurally flexible erbium–anilato MOF

By combining 3,6-N-ditriazolyl-2,5-dihydroxy-1,4-benzoquinone (H₂trz₂An) with NIR-emitting Er^III ions, two different 3D neutral polymorphic frameworks (1a and 1b), differing in the number of uncoordinated water molecules, formulated as [Er₂(trz₂An)₃(H₂O)₄]_n·xH₂O (x = 10, a; x = 7, b), have been obtained. The structure of 1a shows layers with (6,3) topology forming six-membered rings with distorted hexagonal cavities along the bc plane. These 2D layers are interconnected through the N4 atoms of the two pendant arms of the trz₂An linkers, leading to a 3D framework, where neighboring layers are eclipsed along the a axis, with hexagonal channels filled with water molecules. In 1b, layers with (6,3) topology in the [101] plane are present, each Er^III ion being connected to three other Er^III ions through bis-bidentate trz₂An linkers, forming rectangular six-membered cavities. 1a and 1b are multifunctional materials showing coexistence of NIR emission and field-induced slow relaxation of the magnetization. Remarkably, 1a is a flexible MOF, showing a reversible structural phase transition involving shrinkage/expansion from a distorted hexagonal 2D framework to a distorted 3,6-brickwall rectangular 3D structure in [Er₂(trz₂An)₃(H₂O)₂]_n·2H₂O (1a_des). This transition is triggered by a dehydration/hydration process under mild conditions (vacuum/heating to 360 K). The partially dehydrated compound shows a sizeable change in the emission properties and an improvement of the magnetic blocking temperature with respect to the hydrated compound, mainly related to the loss of one water coordination molecule. Theoretical calculations support the experimental findings, indicating that the slight improvement observed in the magnetic properties has its origin in the change of the ligand field around the Er^III ion due to the loss of a water molecule.

Tuning of luminescent and SIM properties is herein reported, in a novel flexible 3D anilato-based Er^III-MOF, displaying reversible shrinkage/expansion from a distorted hexagonal to a 3,6-brickwall rectangular structure.