[Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study.] / Neuropatía periférica, onicólisis y calidad de vida en mujeres con cáncer de mama en tratamiento con taxanos. Estudio longitudinal prospectivo.

OBJECTIVE: Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. METHODS: Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2®. For the relationship of the qualitative variables, the chi-square, Fisher's exact test, Mc's test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. RESULTS: 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ2=11.3; p<0.001 / χ2=13.0; p<0.001) and 38.1% a health related quality of live limited in excessive activities (χ2=10.3; p=0.001). Post-treatment evaluation the 20.9% presented motor neuropathy and 32.6% sensitive neuropathy (χ2=3.57; p=0.059 / χ2=6.23; p=0.013), the 86% onycholisis in upper extremities and lower extremities (χ2=6.07; p=0.048 / χ2=10.1; p=0.006) and 58.5% a health related quality of live limited in excessive activities (χ2=8.47; p=0.014). 6 month later, the initials parameters were not recuperated. CONCLUSIONS: Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause.

OBJETIVO: La neuropatía periférica y la onicólisis son eventos adversos producidos por los taxanos en el cáncer de mama, que perduran incluso habiendo finalizado el tratamiento e influyendo negativamente en la calidad de vida. Los objetivos del estudio fueron describir estos efectos secundarios, midiendo el grado de afectación, y relacionarlos con las dosis de fármaco recibidas. METODOS: Se realizó un estudio observacional, longitudinal prospectivo con muestreo consecutivo inicial de concuenta mujeres con cáncer de mama en tratamiento con docetaxel y/o paclitaxel en el Hospital Universitario Miguel Servet de Zaragoza (Aragón, España). Para la valoración de la neuropatía periférica (motora y sensitiva) se utilizó la escala CTCAE v.5.0 y el test de Semmes Weinsten. La valoración de la calidad de vida relacionada con la salud se midió mediante la escala ECOG. Se realizaron valoraciones previo-durante-post y a los 6 meses de haber finalizado el tratamiento. El análisis estadístico se realizó mediante Jamovi 1.2®. Para la relación de las variables cualitativas se utilizó la chi-cuadrado, el test exacto de Fisher, el test de Mc.Nemar y el test de Odds Ratio. Los efectos se consideraron significativos si p<0,05. RESULTADOS: Se incluyeron finalmente 43 mujeres. Durante el tratamiento, el 9,8% presentó neuropatía motora y el 12,2% neuropatía sensitiva, el 37,2% onicólisis en extremidades superiores y el 39,5% en inferiores (χ2=11,3; p<0,001 / χ2=13,0; p<0,001), y el 38,1% una calidad de vida restringida a actividad exagerada (χ2=10,3; p=0,001). En la valoración postratamiento, el 20,9% presentó neuropatía motora y el 32,6% neuropatía sensitiva (χ2=3,57; p=0,059 / χ2=6,23; p=0,013), el 86% onicólisis en extremidades superiores y el 90,7% en inferiores (χ2=6,07; p=0,048 / χ2=10,1; p=0,006) y el 58,5% al menos una calidad de vida restringida a actividad exagerada (χ2=8,47; p=0,014). A los seis meses no se recuperaron los valores iniciales de evaluación. CONCLUSIONES: Los taxanos repercuten negativamente en la calidad de vida de las mujeres incluso a los seis meses tras finalizar el tratamiento debido a la neuropatía periférica y la onicólisis que provocan.

Neuropatía periférica, onicólisis y calidad de vida en mujeres con cáncer de mama en tratamiento con taxanos. Estudio longitudinal prospectivo / Peripheral neuropathy, onycholysis and health-related quality of life in womens with breast cancer treated with taxanes. Prospective longitudinal study

FUNDAMENTOS: La neuropatía periférica y la onicólisis son eventos adversos producidos por los taxanos en el cáncer de mama, que perduran incluso habiendo finalizado el tratamiento e influyendo negativamente en la calidad de vida. Los objetivos del estudio fueron describir estos efectos secundarios, midiendo el grado de afectación, y relacionarlos con las dosis de fármaco recibidas. MÉTODOS: Se realizó un estudio observacional, longitudinal prospectivo con muestreo consecutivo inicial de concuenta mujeres con cáncer de mama en tratamiento con docetaxel y/o paclitaxel en el Hospital Universitario Miguel Servet de Zaragoza (Aragón, España). Para la valoración de la neuropatía periférica (motora y sensitiva) se utilizó la escala CTCAE v.5.0 y el test de Semmes Weinsten. La valoración de la calidad de vida relacionada con la salud se midió mediante la escala ECOG. Se realizaron valoraciones previo-durante-post y a los 6 meses de haber finalizado el tratamiento. El análisis estadístico se realizó mediante Jamovi 1.2 ®. Para la relación de las variables cualitativas se utilizó la chi-cuadrado, el test exacto de Fisher, el test de Mc.Nemar y el test de Odds Ratio. Los efectos se consideraron significativos si p<0,05. RESULTADOS: Se incluyeron finalmente 43 mujeres. Durante el tratamiento, el 9,8% presentó neuropatía motora y el 12,2% neuropatía sensitiva, el 37,2% onicólisis en extremidades superiores y el 39,5% en inferiores (χ2 =11,3; p<0,001 / χ2 =13,0; p<0,001), y el 38,1% una calidad de vida restringida a actividad exagerada (χ2 =10,3; p=0,001). En la valoración postratamiento, el 20,9% presentó neuropatía motora y el 32,6% neuropatía sensitiva (χ2 =3,57; p=0,059 / χ2 =6,23; p=0,013), el 86% onicólisis en extremidades superiores y el 90,7% en inferiores (χ2 =6,07; p=0,048 / χ2 =10,1; p=0,006) y el 58,5% al menos una calidad de vida restringida a actividad exagerada(χ2=8,47; p=0,014). A los seis meses no se recuperaron los valores iniciales...(AU)

BACKGROUND: Peripheral neuropathy and onycholysis are adverse events produced by taxanes in breast cancer that persist even after the end of treatment and negatively influence quality of life. The objectives of the study were to describe these side effects and the degree of involvement and relating them to the drug doses received. METHODS: Prospective, cross-sectional study of in 50 womens dignosed of breast cancer, treated with docetaxel and paclitaxel in Hospital Universitario Miguel Servet in Zaragoza (Aragón, Spain). CTCAE v.5.0 scale and Semes Weinsten test were used to evaluate peripheral neuropathy and onycholysis. ECOG scale was performed to measure the health-related quality of life. Study variables were evaluated before-during treatment and 1 and 6 months after finish treatment. Statistical analysis was performed using Jamovi 1.2® . For the relationship of the qualitative variables, the chi-square, Fisher’s exact test, Mc’s test were used. Nemar and the Odds Ratio test. Effects were considered significant if p<0.05. RESULTS: 43 subjects were included. During treatment the 9.8 presented motor neuropathy and 12.2% sensitive neuropathy, 37.2% onycholisis in upper extremities and 39.5% in lower extremities (χ2 =11.3; p<0.001 / χ2 =13.0; p<0.001) and 38.1% a health related quality of live limited in excessive activities (χ2 =10.3; p=0.001). Post-treatment evaluation the 20.9% presented motor neuropathy and 32.6% sensitive neuropathy (χ2 =3.57; p=0.059 / χ2 =6.23; p=0.013), the 86% onycholisis in upper extremities and lower extremities (χ2 =6.07; p=0.048 / χ2 =10.1; p=0.006) and 58.5% a health related quality of live limited in excessive activities (χ2 =8.47; p=0.014). 6 month later, the initials parameters were not recuperated. CONCLUSIONS: Taxanes have a negative impact on the health-related quality of life in patients, even 6 months after finishing treatment due to the peripheral neuropathy and onycholysis that they cause.(AU)

Ultrasound-Assisted Extraction of High-Value Fractions from Fruit Industrial Processing Waste.

This work deals with the valorization of fruit industrial processing waste pretreated with two dehydration methods, air oven and lyophilization. Ultrasound-assisted extraction using a sonication probe was selected to recover the high-value fractions. A battery of experiments following a Box−Behnken design was planned to evaluate the effect of the ultrasound amplitude, extraction duration, and temperature on the yield, protein content, phenolic content, and antiradical capacity of the soluble extracts. Operating at a fixed frequency (24 kHz) and solid:water ratio (1:15), the models predicted (significance degree >95%) the maximum extraction conditions of 69.7% amplitude, 53.43 °C, and 12 min for conventionally dehydrated fruit waste. Under these processing conditions, 52.6% extraction yield was achieved, with a protein content of 0.42 mg/g, total phenolic content of 116.42 mg GAE/g, and antioxidant capacity of 44.95 mg Trolox/g. Similar yields (53.95%) and a notably higher protein content (0.69 mg/g), total phenolic content (135.32 mg GAE/g), and antioxidant capacity (49.52 mg Trolox/g) were identified for lyophilized fruit waste. This treatment required a longer dehydration pretreatment duration (double), higher ultrasound amplitude (80%), and higher extraction temperature (70 °C), but shorter extraction time (4 min). These outcomes highlighted the important impact of the dehydration method on the valorization of the tested waste, with conventional drying saving costs, but the lyophilization procedure enhancing the bioactive features of the waste.

Pressurized Hot Water Extraction and Bio-Hydrogels Formulation with Aristotelia chilensis [Mol.] Stuntz Leaves.

Aristotelia chilensis is a plant rich in phenolics and other bioactive compounds. Their leaves are discarded as waste in the maqui berry industry. A new application of these wastes is intended by the recovery of bioactive compounds using pressurized hot water extraction with conventional or microwave heating. Both technologies have been selected for their green character regarding the type of solvent and the high efficiency in shorter operation times. Extractions were performed in the temperature range 140-200 °C with a solid/liquid ratio of 1:15 (w:w). The extracts' total phenolic content, antioxidant capacity, and saccharides content obtained with both heating methods were measured. Additionally, the thermo-rheological properties of the gelling matrix enriched with these extracts were analyzed. Optimum conditions for lyophilized extracts were found with conventional heating, at 140 °C and 20 min extraction; 250.0 mg GAE/g dry extract and 1321.5 mg Trolox/g dry extract. Close to optimum performance was achieved with microwave heating in a fraction of the time (5 min) at 160 °C (extraction), yielding extracts with 231.9 mg GAE/g dry extract of total phenolics and antiradical capacity equivalent to 1176.3 mg Trolox/g dry extract. Slightly higher antioxidant values were identified for spray-dried extracts (between 5% for phenolic content and 2.5% for antioxidant capacity). The extracts obtained with both heating methods at 200 °C contained more than 20% oligosaccharides, primarily glucose. All the formulated gelling matrices enriched with the obtained extracts displayed intermediate gel strength properties. The tested technologies efficiently recovered highly active antioxidant extracts, rich in polyphenolics, and valuable for formulating gelling matrices with potential applicability in foods and other products.

Permanently polarized hydroxyapatite for selective electrothermal catalytic conversion of carbon dioxide into ethanol.

Conversion of CO2 into valuable chemicals is not only a very challenging topic but also a socially demanding issue. In this work, permanently polarized hydroxyapatite obtained using a thermal stimulated polarization process is proposed as a highly selective catalyst for green production of ethanol starting from CO2 and CH4.

Treatment of Hepatic Fibrosis in Mice Based on Targeted Plasmonic Hyperthermia.

Liver fibrosis is a major health problem with multiple associated complications, which, to date, has no effective treatment. Hepatic stellate cells are the main responsible cells for fibrosis formation; upon their activation, excess accumulation of extracellular matrix and collagen deposits occurs. The mitogen platelet-derived growth factor (PDGF) and its receptor ß (PDGFRß) play a major role in hepatic stellate cells activation and are, therefore, promising targets for antifibrotic therapies. Gold nanorods hold great potential for diseased liver treatments, since their passive hepatic accumulation enhances active targeting strategies, hence increasing therapeutic efficiency. In addition, gold nanorods have photothermal properties that, combined with specific cell delivery, can be exploited to induce localized near-infrared light-mediated thermal ablation. Here, we demonstrate that gold nanorods coated with anti-PDGFRß specifically target activated hepatic stellate cells in vivo. Additionally, gold nanorods-PDGFRß-mediated photothermal therapy decreases fibrosis, hepatic inflammation, and hepatocyte injury in the experimental model of CCl4-induced liver fibrosis in mice.

Electrically Polarized Hydroxyapatite: Influence of the Polarization Process on the Microstructure and Properties.

Semipermanently polarized hydroxyapatite, named SP/HAp(w), is obtained by applying a constant dc electric field of 1-10 kV/cm at 300-850 °C to the samples previously sintered in water vapor, while permanently polarized hydroxyapatite, PP/HAp(a), is produced by applying a dc electric field of 3 kV/cm at 1000 °C to the samples sintered in air. SP/HAp(w) has been used for biomedical applications, while PP/HAp(a) has been proved to be a valuable catalyst for N2 and CO2 fixation. In this work, structural differences between SP/HAp(w) and PP/HAp(a) have been ascertained using Raman microscopy, wide-angle X-ray diffraction, scanning electronic microscopy, high-resolution transmission electron microscopy, and grazing incidence X-ray diffraction. Results prove the existence of crystal distortion in the form of amorphous calcium phosphate and ß-tricalcium phosphate (ß-TCP) phases close to the surface because of the atmosphere used in the sintering process. The existence of an amorphous layer in the surface and the phase transition through ß-TCP of SP/HAp(w) are the structural factors responsible for the differences with respect to PP/HAp(a). Moreover, a superstructure has been identified in PP/HAp(a) samples, which could be another structural factor associated with enhanced conductivity, permanent polarization, and catalytic activity of this material.

Quantification of gold nanoparticle accumulation in tissue by two-photon luminescence microscopy.

Nanomedicine has emerged as a promising strategy to address some of the limitations of traditional biomedical sensing, imaging and therapy modalities. Its applicability and efficacy are, in part, hindered by the difficulty in both controllably delivering nanoparticles to specific regions and accurately monitoring them in tissue. Gold nanoparticles are among the most extensively used inorganic nanoparticles which benefit from high biocompatibility, flexible functionalization, strong and tunable resonant absorption, and production scalability. Moreover, their capability to enhance optical fields at their plasmon resonance enables local boosting of non-linear optical processes, which are otherwise very inefficient. In particular, two-photon induced luminescence (TPL) in gold offers high signal specificity for monitoring gold nanoparticles in a biological environment. In this article, we demonstrate that TPL microscopy provides a robust sub-micron-resolution technique able to quantify accumulated gold nanorods (GNRs) both in cells and in tissues. First, the temporal accumulation of GNRs with two different surface chemistries was measured in 786-O cells during the first 24 hours of incubation, and at different nanoparticle concentrations. Subsequently, GNR accumulation in mice, 6 h and 24 hours after tail vein injection, was quantified by TPL microscopy in biopsied tissue from kidney, spleen, liver and clear cell renal cell carcinoma (ccRCC) tumors, in good agreement with inductively coupled mass spectroscopy. Our data suggest that TPL microscopy stands as a powerful tool to understand and quantify the delivery mechanisms of gold nanoparticles, highly relevant to the development of future theranostic medicines.

Non-invasive and quantitative in vivo monitoring of gold nanoparticle concentration and tissue hemodynamics by hybrid optical spectroscopies.

Owing to their unique combination of chemical and physical properties, inorganic nanoparticles show a great deal of potential as suitable agents for early diagnostics and less invasive therapies. Yet, their translation to the clinic has been hindered, in part, by the lack of non-invasive methods to quantify their concentration in vivo while also assessing their effect on the tissue physiology. In this work, we demonstrate that diffuse optical techniques, employing near-infrared light, have the potential to address this need in the case of gold nanoparticles which support localized surface plasmons. An orthoxenograft mouse model of clear cell renal cell carcinoma was non-invasively assessed by diffuse reflectance and correlation spectroscopies before and over several days following a single intravenous tail vein injection of polyethylene glycol-coated gold nanorods (AuNRs-PEG). Our platform enables to resolve the kinetics of the AuNR-PEG uptake by the tumor in quantitative agreement with ex vivo inductively coupled plasma mass spectroscopy. Furthermore, it allows for the simultaneous monitoring of local tissue hemodynamics, enabling us to conclude that AuNRs-PEG do not significantly alter the animal physiology. We note that the penetration depth of this current probe was a few millimeters but can readily be extended to centimeters, hence gaining clinical relevance. This study and the methodology presented here complement the nanomedicine toolbox by providing a flexible platform, extendable to other absorbing agents that can potentially be translated to human trials.

Plasmon-Based Biofilm Inhibition on Surgical Implants.

The insertion of an implant in the body of a patient raises the risk of a posterior infection and formation of a biofilm, which can have critical consequences on the patient's health and be associated with a high sanitary cost. While antibacterial agents can be used to prevent the infection, such a strategy is time-limited and causes bacteria resistance. As an alternative to biochemical approaches, we propose here to use light-induced local hyperthermia with plasmonic nanoparticles. This strategy is implemented on surgical meshes, extensively used in the context of hernia repairing, one of the most common general surgeries. Surgical meshes were homogeneously coated with gold nanorods designed to efficiently convert near-infrared light into heat. The modified mesh was exposed to a biofilm of Staphylococcus aureus ( S. aureus) bacteria before being treated with a train of light pulses. We systematically study how the illumination parameters, namely fluence, peak intensity and pulse length, influence the elimination of attached bacteria. Additionally, fluorescence confocal microscopy provides us some insight on the mechanism involved in the degradation of the biofilm. This proof-of-principle study opens a new set of opportunities for the development of novel disinfection approaches combining light and nanotechnology.

Self-Calibrating On-Chip Localized Surface Plasmon Resonance Sensing for Quantitative and Multiplexed Detection of Cancer Markers in Human Serum.

The need for point-of-care devices able to detect diseases early and monitor their status, out of a lab environment, has stimulated the development of compact biosensing configurations. Whereas localized surface plasmon resonance (LSPR) sensing integrated into a state-of-the-art microfluidic chip stands as a promising approach to meet this demand, its implementation into an operating sensing platform capable of quantitatively detecting a set of molecular biomarkers in an unknown biological sample is only in its infancy. Here, we present an on-chip LSPR sensor capable of performing automatic, quantitative, and multiplexed screening of biomarkers. We demonstrate its versatility by programming it to detect and quantify in human serum four relevant human serum protein markers associated with breast cancer.

Two-color dark-field (TCDF) microscopy for metal nanoparticle imaging inside cells.

Noble metal nanoparticles (NPs) supporting localized surface plasmon resonances are widely used in the context of biotechnology as optical and absorption contrast agents with great potential applicability to both diagnostics and less invasive therapies. In this framework, it is crucial to have access to simple and reliable microscopy techniques to monitor the NPs that have internalized into cells. While dark field (DF) microscopy takes advantage of the enhanced NP scattering at their plasmon resonance, its use in cells is limited by the large scattering background from the internal cell compartments. Here, we report on a novel two-color dark field microscopy that addresses these limitations by significantly reducing the cell scattering contribution. We first present the technique and demonstrate its enhanced contrast, specificity and reliability for NP detection compared to a standard optical dark field. We then demonstrate its potential suitability in two different settings, namely wide-field parallel screening of circulating cells in microfluidic chips and high-resolution tracking of internalized NPs in cells. These proof of principle experiments show a promising capability of this approach with possible extension to other kinds of targeted systems like bacteria and vesicles.

Optimum morphology of gold nanorods for light-induced hyperthermia.

Owing to their unique chemical and physical properties, colloidal gold nanoparticles have prompted a wide variety of biocompatible nano-agents for cancer imaging, diagnosis and treatment. In this context, biofunctionalized gold nanorods (AuNRs) are promising candidates for light-induced hyperthermia, to cause local and selective damage in malignant tissue. Yet, the efficacy of AuNR-based hyperthermia is highly dependent on several experimental parameters; in particular, the AuNR morphology strongly affects both physical and biological processes. In the present work, we systematically study the influence of different structural parameters like the AuNR aspect ratio, length and molecular weight on in vitro cytotoxicity, cellular uptake and heat generation efficiency. Our results enable us to identify the optimum AuNR morphology to be used for in vivo hyperthermia treatment.

On-a-chip Biosensing Based on All-Dielectric Nanoresonators.

Nanophotonics has become a key enabling technology in biomedicine with great promises in early diagnosis and less invasive therapies. In this context, the unique capability of plasmonic noble metal nanoparticles to concentrate light on the nanometer scale has widely contributed to biosensing and enhanced spectroscopy. Recently, high-refractive index dielectric nanostructures featuring low loss resonances have been proposed as a promising alternative to nanoplasmonics, potentially offering better sensing performances along with full compatibility with the microelectronics industry. In this letter we report the first demonstration of biosensing with silicon nanoresonators integrated in state-of-the-art microfluidics. Our lab-on-a-chip platform enables detecting Prostate Specific Antigen (PSA) cancer marker in human serum with a sensitivity that meets clinical needs. These performances are directly compared with its plasmonic counterpart based on gold nanorods. Our work opens new opportunities in the development of future point-of-care devices toward a more personalized healthcare.

LSPR chip for parallel, rapid, and sensitive detection of cancer markers in serum.

Label-free biosensing based on metallic nanoparticles supporting localized surface plasmon resonances (LSPR) has recently received growing interest (Anker, J. N., et al. Nat. Mater. 2008, 7, 442-453). Besides its competitive sensitivity (Yonzon, C. R., et al. J. Am. Chem. Soc. 2004, 126, 12669-12676; Svendendahl, M., et al. Nano Lett. 2009, 9, 4428-4433) when compared to the surface plasmon resonance (SPR) approach based on extended metal films, LSPR biosensing features a high-end miniaturization potential and a significant reduction of the interrogation device bulkiness, positioning itself as a promising candidate for point-of-care diagnostic and field applications. Here, we present the first, paralleled LSPR lab-on-a-chip realization that goes well beyond the state-of-the-art, by uniting the latest advances in plasmonics, nanofabrication, microfluidics, and surface chemistry. Our system offers parallel, real-time inspection of 32 sensing sites distributed across 8 independent microfluidic channels with very high reproducibility/repeatability. This enables us to test various sensing strategies for the detection of biomolecules. In particular we demonstrate the fast detection of relevant cancer biomarkers (human alpha-feto-protein and prostate specific antigen) down to concentrations of 500 pg/mL in a complex matrix consisting of 50% human serum.

Design of multifunctional gold nanoparticles for in vitro and in vivo gene silencing.

Over the past decade, the capability of double-stranded RNAs to interfere with gene expression has driven new therapeutic approaches. Since small interfering RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA interference (RNAi), efforts were directed toward the development of efficient delivery systems to preserve siRNA bioactivity throughout the delivery route, from the administration site to the target cell. Here we provide evidence of RNAi triggering, specifically silencing c-myc protooncogene, via the synthesis of a library of novel multifunctional gold nanoparticles (AuNPs). The efficiency of the AuNPs is demonstrated using a hierarchical approach including three biological systems of increasing complexity: in vitro cultured human cells, in vivo invertebrate (freshwater polyp, Hydra ), and in vivo vertebrate (mouse) models. Our synthetic methodology involved fine-tuning of multiple structural and functional moieties. Selection of the most active functionalities was assisted step-by-step through functional testing that adopted this hierarchical strategy. Merging these chemical and biological approaches led to a safe, nonpathogenic, self-tracking, and universally valid nanocarrier that could be exploited for therapeutic RNAi.

Protamine and chloroquine enhance gene delivery and expression mediated by RNA-wrapped single walled carbon nanotubes.

The use of non-viral vectors as delivery systems in gene therapy has been extensively studied recently owing to their advantages over viral vectors. Here, we propose a new gene delivery system based on the use of RNA-wrapped single-walled carbon nanotubes (SWCNTs) complexed with the cationic protein, protamine and the drug chloroquine. Protamine was selected as a cationic protein acting as bridge between negatively charged RNA-wrapped SWCNTs and plasmid DNA. Protamine also contains a nuclear localization signal which enhances the expression of the transfected gene. The drug chloroquine, a lysosomotropic compound which has been reported to increase the transfection efficiency, was attached to RNA-wrapped SWNTs by ionic interactions. The simultaneous delivery of the drug chloroquine with plasmid DNA clearly showed an enhanced gene delivery and expression. The levels of gene expression were quantified using the luciferase reporter gene as model. Optimal conditions for transfection and gene expression were obtained and cytoxicity of the carbon nanotube complexes measured. The optimal complexes were shown to efficiently deliver plasmid DNA for efficient gene expression and may thereby be useful as gene delivery systems for gene therapy.

Modification of plasmid DNA topology by 'histone-mimetic' gold nanoparticles.

AIMS: Our aim is to explore whether gold nanoparticles (AuNPs) functionalized with a carboxylated polyethylene glycol (PEG) and protamine (AuNP@PEG@Prot) can modulate - enhance or restrain - DNA condensation, altering DNA conformation and inducing structural changes. Understanding how these nanoconjugates modulate DNA structure, size and shape of DNA condensates, and enable control over the resulting 3D structures is of major biological and therapeutic importance. MATERIALS & METHODS: Citrate-AuNPs were covered with a dense layer of a hetero-functional octa(ethylene glycol) (SH-EG(8)-COOH). Conjugation of protamine to the AuNP@PEG was achieved by taking advantage of the carboxylated surface previously generated on the surface of the NP and the remaining amino groups from the protamine, using carbodiimide and N-hydroxysulfosuccinimide coupling reactions. RESULTS & CONCLUSION: AuNP@PEG@Prot modulates the structure and topology of DNA, not only for condensation, but also for decondensation, via formation of higher quantities of dimers and multimers, when compared with AuNP@PEG and free protamine.

Selective peracetic acid determination in the presence of hydrogen peroxide using a label free enzymatic method based on catalase.

Peracetic acid (PAA) is selectively determined in the presence of hydrogen peroxide (H(2)O(2)) by using the self-indicating UV-Vis molecular absorption properties of catalase. The PAA reacts with the protein giving an intermediate (Cat-I) which is reduced back by the amino acid core surrounding the heme group. Since the original form of the enzyme and the Cat-I have different UV-Vis absorption properties, the absorbance changes can be used for PAA determination. The H(2)O(2)/catalase reaction is extremely fast so that neither Cat-I compound nor kinetic interferences are observed. The method permits PAA determination in the 5 × 10(-7) to 1.5 × 10(-5) M range, the reproducibility being between 1% and 10%. Using this method, PAA has been successfully determined in water samples treated with commercial PAA/H(2)O(2) biocides. A theoretical study has also been carried out for obtaining a mathematical model able to analytically describe the process.

The environmental effect on the fluorescence intensity in solution. An analytical model.

In this paper a mathematical model describing the non-specific interactions of the medium surrounding a fluorophore on its fluorescence intensity is proposed. The model, which has been developed for quantitative analytical applications, is based on the following general ideas: (1) the medium affects the fluorescence quantum yield across the non-radiative decay constant (k(nr)); (2) the k(nr) can be simplified to the singlet-to-triplet intersystem crossing (k(ISC)) constants; (3) k(ISC) follows the energy gap law and then depends on the singlet and triplet energy difference, and (4) the medium, due to solvation, changes the energy of both excited levels (singlet and triplet), then the constants and finally the fluorescence intensity. In our model, the strength of the fluorophore solvation by the solvent (represented by its refraction index, n, dielectric constant, epsilon, and electric charge) changes the singlet (excited)-to-fundamental and the singlet-to-triplet energy gaps, thus the k(ISC) and k(IC) (internal conversion constant) values and in consequence the fluorescence quantum yield. The final model relates the fluorescence intensity (F) with the solvent dielectric constant and refraction index. Finally, the model is particularized for the case of a medium composed of a solvent and a solute, obtaining an F-to-solute concentration relationship and enabling this fact to be used for analytical applications. The very first experimental data are shown demonstrating the fulfilment of this model.