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Treatment failure in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2) is associated mainly to the upregulation of human epidermal growth factor receptor 3 (HER3) oncoprotein linked to chemoresitence. Therefore, to increase patient survival, here a multimodal theranostic nanoplatform targeting both HER2 and HER3 is developed. This consists of doxorubicin-loaded branched gold nanoshells functionalized with the near-infrared (NIR) fluorescent dye indocyanine green, a small interfering RNA (siRNA) against HER3, and the HER2-specific antibody Transtuzumab, able to provide a combined therapeutic outcome (chemo- and photothermal activities, RNA silencing, and immune response). In vitro assays in HER2+ /HER3+ SKBR-3 breast cancer cells have shown an effective silencing of HER3 by the released siRNA and an inhibition of HER2 oncoproteins provided by Trastuzumab, along with a decrease of the serine/threonine protein kinase Akt (p-AKT) typically associated with cell survival and proliferation, which helps to overcome doxorubicin chemoresistance. Conversely, adding the NIR light therapy, an increment in p-AKT concentration is observed, although HER2/HER3 inhibitions are maintained for 72 h. Finally, in vivo studies in a tumor-bearing mice model display a significant progressively decrease of the tumor volume after nanoparticle administration and subsequent NIR light irradiation, confirming the potential efficacy of the hybrid nanocarrier.
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Neoplasias de la Mama , Nanocáscaras , Humanos , Animales , Ratones , Femenino , Neoplasias de la Mama/metabolismo , Proteínas Proto-Oncogénicas c-akt , Oro , Receptor ErbB-2/genética , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , ARN Interferente Pequeño , Línea Celular TumoralRESUMEN
Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death.
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Hipertermia Inducida , Nanotubos , Neoplasias , Humanos , Oro , Células HeLa , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , FototerapiaRESUMEN
The administration of small interfering RNA (siRNA) is a very interesting therapeutic option to treat genetic diseases such as Alzheimer's or some types of cancer, but its effective delivery still remains a challenge. Herein, Au nanorod (GNR)-based platforms functionalized with polyelectrolyte layers were developed and analyzed as potential siRNA nanocarriers. The polymeric layers were successfully assembled on the particle surfaces by means of the layer-by-layer assembly technique through the alternating deposition of oppositely charged poly(styrene)sulfonate, PSS, poly(lysine), PLL, and siRNA biopolymers, with a final hyaluronic acid layer in order to provide the nanoconstructs with a potential targeting ability as well as colloidal stability in physiological medium. Once the hybrid nanocarriers were obtained, the cargo release, their colloidal stability in physiological-relevant media, cytotoxicity, cellular internalization and uptake, and knockdown activity were studied. The present hybrid particles release the genetic material inside cells by means of a protease-assisted and/or a light-triggered release mechanism in order to control the delivery of the oligonucleotides on demand. In addition, the hybrid nanovectors were observed to be nontoxic to cells and could efficiently deliver the genetic material in the cell cytoplasms. The GNR-based nanocarriers proposed here can provide a suitable environment to load and protect a sufficient amount of the genetic material to allow an efficient and sustained knockdown gene expression for long (up to 93% for 72 h), thanks to the slow degradation of PLL, without the observation of adverse side toxic effects. It was also found that the silencing activity was enhanced with the number of siRNA layers assembled in the nanoplatforms.
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Portadores de Fármacos/química , Nanopartículas del Metal/química , Neoplasias/terapia , ARN Interferente Pequeño/administración & dosificación , Tratamiento con ARN de Interferencia/métodos , Técnicas de Silenciamiento del Gen , Genes Reporteros/genética , Oro/química , Proteínas Fluorescentes Verdes/genética , Células HeLa , Humanos , Nanotubos/química , Neoplasias/genética , Polilisina/química , Poliestirenos , ARN Interferente Pequeño/genéticaRESUMEN
Gold nanorods (AuNRs) have attracted attention in the field of biomedicine, particularly for their potential as photothermal agents capable of killing tumor cells by photothermic ablation. In this study, the synthesis of novel AuNRs stabilized with thiolated pectin (AuNR@SH-PEC) is reported. To achieve this, thiolated pectin (SH-PEC) was obtained by chemically binding cysteamine motifs to the pectin backbone. The success of the reaction was ascertained using FTIR-ATR. Subsequently, the SH-PEC was used to coat and stabilize the surface of AuNRs (AuNR@SH-PEC). In this context, different concentrations of SH-PEC (0.25, 0.50, 1.0, 2.0, 4.0, and 8.0 mg/mL) were added to 0.50 mL of AuNRs suspended in CTAB, aiming to determine the experimental conditions under which AuNR@SH-PEC maintains stability. The results show that SH-PEC effectively replaced the CTAB adsorbed on the surface of AuNRs, enhancing the stability of AuNRs without affecting their optical properties. Additionally, scanning electron and atomic force microscopy confirmed that SH-PEC is adsorbed into the surface of the AuNRs. Importantly, the dimension size (60 × 15 nm) and the aspect ratio (4:1) remained consistent with those of AuNRs stabilized with CTAB. Then, the photothermal properties of gold nanorods were evaluated by irradiating the aqueous suspension of AuNR@SH-PEC with a CW laser (808 nm, 1 W). These results showed that photothermal conversion efficiency is similar to the photothermal conversion observed for AuNR-CTAB. Lastly, the cell viability assays confirmed that the SH-PEC coating enhanced the biocompatibility of AuNR@SH-PEC. Most important, the viability cell assays subjected to laser irradiation in the presence of AuNR@SH-PEC showed a decrease in the cell viability relative to the non-irradiated cells. These results suggest that AuNRs stabilized with thiolated pectin can potentially be exploited in the implementation of photothermal therapy.
RESUMEN
Atherosclerosis is an underlying risk factor in cardiovascular diseases (CVDs). The combination of drugs with microRNAs (miRNA) inside a single nanocarrier has emerged as a promising anti-atherosclerosis strategy to achieve the exploitation of their complementary mechanisms of action to achieve synergistic therapeutic effects while avoiding some of the drawbacks associated with current systemic statin therapies. We report the development of nanometer-sized polymeric PLGA nanoparticles (NPs) capable of simultaneously encapsulating and delivering miRNA-124a and the statin atorvastatin (ATOR). The polymeric NPs were functionalized with an antibody able to bind to the vascular adhesion molecule-1 (VCAM1) overexpressed in the inflamed arterial endothelium. The dual-loaded NPs were non-toxic to cells in a large range of concentrations, successfully attached overexpressed VCAM receptors and released the cargoes in a sustainable manner inside cells. The combination of both ATOR and miRNA drastically reduced the levels of proinflammatory cytokines such as IL-6 and TNF-α and of reactive oxygen species (ROS) in LPS-activated macrophages and vessel endothelial cells. In addition, dual-loaded NPs precluded the accumulation of low-density lipoproteins (LdL) inside macrophages as well as morphology changes to a greater extent than in single-loaded NPs. The reported findings validate the present NPs as suitable delivery vectors capable of simultaneously targeting inflamed cells in atherosclerosis and providing an efficient approach to combination nanomedicines.
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Magnetic nanowires were obtained through the in situ synthesis of magnetic material by Fe-controlled nanoprecipitation in the presence of two different protein (human serum albumin (HSA) and lysozyme (Lys)) fibrils as biotemplating agents. The structural characteristics of the biotemplates were transferred to the hybrid magnetic wires. They exhibited excellent magnetic properties as a consequence of the 1D assembly and fusion of magnetite nanoparticles as ascertained by SQUID magnetometry. Prompted by these findings, we also checked their potential applicability as MRI contrast agents. The magnetic wires exhibited large r(2)* relaxivities and sufficient contrast resolution even in the presence of an extremely small amount of Fe in the magnetic hybrids, which would potentially enable their use as T(2) contrast imaging agents.
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Medios de Contraste/química , Magnetismo , Nanocables/química , Proteínas/química , Algoritmos , Humanos , Imagen por Resonancia Magnética , Muramidasa/química , Proteínas/ultraestructura , Albúmina Sérica/químicaRESUMEN
The fibrillation propensity of the multidomain protein human serum albumin (HSA) has been analyzed under physiological and acidic conditions at room and elevated temperatures with varying ionic strengths by different spectroscopic techniques. The kinetics of fibril formation under the different solution conditions and the structures of resulting fibrillar aggregates were also determined. In this way, we have observed that fibril formation is largely affected by electrostatic shielding: at physiological pH, fibrillation is progressively more efficient and faster in the presence of up to 50 mM NaCl; meanwhile, at larger salt concentrations, excessive shielding and further enhancement of the solution hydrophobicity might involve a change in the energy landscape of the aggregation process, which makes the fibrillation process difficult. In contrast, under acidic conditions, a continuous progressive enhancement of HSA fibrillation is observed as the electrolyte concentration in solution increases. Both the distinct ionization and initial structural states of the protein before incubation may be the origin of this behavior. CD, FT-IR, and tryptophan fluorescence spectra seem to confirm this picture by monitoring the structural changes in both protein tertiary and secondary structures along the fibrillation process. On the other hand, the fibrillation of HSA does not show a lag phase except at pH 3.0 in the absence of added salt. Finally, differences in the structure of the intermediates and resulting fibrils under the different conditions are also elucidated by TEM and FT-IR.
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Albúmina Sérica/metabolismo , Electricidad Estática , Amiloide/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Cinética , Microscopía Electrónica de Transmisión , Concentración Osmolar , Unión Proteica , Albúmina Sérica/química , Soluciones , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Protein aggregation has a multitude of consequences ranging from affecting protein expression to its implication in different diseases. Of recent interest is the specific form of aggregation leading to the formation of amyloid fibrils, structures associated with diseases such as Alzheimer's disease. These fibrils can further associate in other more complex structures such as fibrillar gels, plaques, or spherulitic structures. In the present work, we describe the physical and structural properties of additional supraself-assembled structures of human serum albumin under solution conditions in which amyloid-like fibrils are formed. We have detected the formation of ordered aggregates of amyloid fibrils, i.e., spherulites which possess a radial arrangement of the fibrils around a disorganized protein core and sizes of several micrometers by means of polarized optical microscopy, laser confocal microscopy, and transmission electron microscopy. These spherulites are detected both in solution and embedded in an isotropic matrix of fibrillar gels. In this regard, we have also noted the formation of protein gels when the protein concentration and/or ionic strength exceds a threshold value (the gelation point) as observed by rheometry. Fibrillar gels are formed through intermolecular nonspecific association of amyloid fibrils at a pH far away from the isolectric point of the protein where protein molecules seem to display a "solid-like" behavior due to the existence of non-DLVO (Derjaguin-Landau-Verwey-Overbeck) intermolecular repulsive forces. As the solution ionic strength increases, a coarsening of this type of gel is observed by environmental scanning microscopy. In contrast, at pH close to the protein isoelectric point, particulate gels are formed due to a faster aggregation process, which does not allow substantial structural reorganization to enable the formation of ordered structures. This behavior also additionally corroborates that the existence of particulates might also be a generic property of all polypeptide chains as amyloid fibril formation under suitable conditions.
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Amiloide/química , Albúmina Sérica/química , Soluciones/química , Humanos , Concentración de Iones de Hidrógeno , Microscopía de Fuerza Atómica , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
The complexation process and underlying mechanisms that rule the interaction of DNA with the cationic block copolymer Tetronic T901 to form polyplexes and their potential transfection efficiency have been studied under different solution conditions. We noted that T901 favors the formation of self-assembled structures with partially condensed DNA at smaller polymer concentrations than other Pluronic™/Tetronic™-type copolymers previously analysed. The observed polyplexes display sizes from the nano- to the micro- range as derived from DLS, electronic and optical microscopies. Also, copolymer micelles are observed at concentrations below the copolymer critical micellar concentration (cmc) induced by the presence of DNA. The complexation process is dependent on solution conditions, with electrostatic and ionic interactions being more important at acidic pH thanks to the predominant diprotonated form of the block copolymer which is less aggregation-prone, whilst dispersive forces are increasingly enhanced under basic conditions or when rising the solution temperature. Whatever the case, the complexation is mainly governed by entropic contributions, as denoted from ITC data. In vitro transfection experiments after complexing T901 with a pDNA encoding the expression of green fluorescein protein, GFP, show a relative successful fluorescence of transfected HeLa cells, which confirms the uptake, internalization and release of the genetic material within the cells at suitable [N]/[P] ratios with relatively low cytotoxicity. Despite the observed successful outcomes, the obtained transfection efficacies are slightly lower than those obtained with Lipofectamine2000, so further optimization of the polyplex formation conditions is envisaged in future studies.
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ADN/química , Etilenodiaminas/química , Nanopartículas/química , Polietilenglicoles/química , Glicoles de Propileno/química , Supervivencia Celular , Entropía , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HeLa , Humanos , Micelas , Tamaño de la Partícula , Electricidad Estática , Propiedades de Superficie , TransfecciónRESUMEN
In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2/HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules. To do that, DOXO could be successfully loaded onto the hybrid nanoconstructs through electrostatic interactions with high efficiencies of up to ca. 78.3 ± 6.9% for the first formed drug layer and 56 ± 13% for the second one, with a total efficiency for the whole system [(PSS/DOXO/PLL)2/HA-coated NRs] of ca. 65.7 ± 1.4%. Nanohybrid internalization was observed to be enhanced by the outer HA layer, which is able to target the CD44 receptors widely overexpressed in some types of cancers as lung, breast, or ovarian ones. Hence, these nanohybrid systems might be versatile nanoplatforms to simultaneously deliver sufficient heat for therapeutic plasmonic hyperthermia and the anticancer drug. Two controlled mechanisms were proposed to modulate the release of the chemodrug, one by means of the enzymatic degradable character of the PLL layer and another by the modulation of the interactions between the polymeric layers through the exploitation of the optical properties of the hybrid particles under near infrared (NIR) laser irradiation. The combination of this bimodal therapeutic approach exerted a synergistic cytotoxic effect on both HeLa and MDA-MB-231 cancer cells in vitro. Cell death mechanisms were also analyzed, elucidating that plasmonic photothermal therapy induces cell necrosis, whereas DOXO activates the cell apoptotic pathway. Therefore, the present NIR laser-induced targeted cancer thermo/chemotherapy represents a novel targeted anticancer strategy with easy control on demand and suitable therapeutic efficacy.
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In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections.
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Antifúngicos/farmacología , Micelas , Óxidos/farmacología , Polienos/farmacología , Polietilenglicoles/farmacología , Polímeros/farmacología , Antifúngicos/química , Candida albicans/efectos de los fármacos , Candida albicans/fisiología , Preparaciones de Acción Retardada , Geles , Óxidos/química , Polienos/química , Polietilenglicoles/química , Polímeros/químicaRESUMEN
We report the synthesis of branched gold nanoshells (BGNS) through a seeded-growth surfactant-less method. This was achieved by decorating chitosan-Pluronic F127 stabilized poly(lactic-co-gycolic) acid nanoparticles (NPs) with Au seeds (NP-seed), using chitosan as an electrostatic self-assembling agent. Branched shells with different degrees of anisotropy and optical response were obtained by modulating the ratios of HAuCl4/K2CO3 growth solution, ascorbic acid (AA) and NP-seed precursor. Chitosan and AA were crucial in determining the BGNS size and structure, acting both as coreductants and structure directing growth agents. Preliminary cytotoxicity experiments point to the biocompatibility of the obtained BGNS, allowing their potential use in biomedical applications. In particular, these nanostructures with "hybrid" compositions, which combine the features of gold nanoshells and nanostars showed a better performance as surface enhanced Raman spectroscopy probes in detecting intracellular cell components than classical smoother nanoshells.
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Quitosano/química , Oro/química , Ácido Láctico/química , Nanocáscaras/química , Poloxámero/química , Ácido Poliglicólico/química , Nanocáscaras/ultraestructura , Tamaño de la Partícula , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Propiedades de SuperficieRESUMEN
Amphiphilic block copolymers have emerged during last years as a fascinating substrate material to develop micellar nanocontainers able to solubilize, protect, transport, and release under external or internal stimuli different classes of cargos to diseased cells or tissues. However, this class of materials can also induce biologically relevant actions, which complement the therapeutic activity of their cargo molecules through their mutual interactions with biologically relevant entities (cellular membranes, proteins, organelles...); these interactions at the same time, are regulated by the nature, conformation, and state of the copolymeric chains. For these reasons, in this paper we investigated the self-assembly process and physico-chemcial properties of two reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers, BO14EO378BO14 and BO21EO385BO21, which have been recently found to be very useful as drug delivery nanovehicles and biological response modifiers under certain conditions (A. Cambón et al. Int. J. Pharm. 2013, 445, 47-57) in order to obtain a clear picture of the solution behavior of this class or block copolymers and to understand their biological activity. These block copolymers are characterized by possessing long BO blocks and extremely lengthy central EO ones, which provide them with a rich rheological behavior characterized by the formation of flowerlike micelles with sizes ranging from 20 to 40 nm in aqueous solution and the presence of intermicellar bridging even at low copolymers concentrations as denoted by atomic force microscopy. Bridging is also clearly observed by analyzing the rheological response of these block copolymers both storage and loss moduli upon changes on time, temperature, and or concentration. Strikingly, the relatively wide Poisson distribution of the polymeric chains make the present copolymers behave rather distinctly to conventional associative thickeners. The observed rich rheological behavior and their tunability also make these copolymers promising materials to configure drug gelling depots.
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Compuestos Epoxi/química , Óxido de Etileno/química , Polímeros/química , Portadores de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Polimerizacion , Reología , Temperatura , TermodinámicaRESUMEN
Two new poly(ethylene oxide)-poly(styrene oxide) triblock copolymers (PEO-PSO-PEO) with optimized block lengths selected on the basis of previous studies were synthesized with the aim of achieving a maximal solubilization ability and a suitable sustained release, while keeping very low material expense and excellent aqueous copolymer solubility. The self-assembling and gelling properties of these copolymers were characterized by means of light scattering, fluorescence spectroscopy, transmission electron microscopy, and rheometry. Both copolymers formed spherical micelles (12-14 nm) at very low concentrations. At larger concentration (>25 wt%), copolymer solutions showed a rich phase behavior, with the appearance of two types of rheologically active (more viscous) fluids and of physical gels depending on solution temperature and concentration. The copolymer behaved notably different despite their relatively similar block lengths. The ability of the polymeric micellar solutions to solubilize the antifungal drug griseofulvin was evaluated and compared to that reported for other structurally-related block copolymers. Drug solubilization values up to 55 mg g(-1) were achieved, which are greater than those obtained by previously analyzed poly(ethylene oxide)-poly(styrene oxide), poly(ethylene oxide)-poly(butylene oxide), and poly(ethylene oxide)-poly(propylene oxide) block copolymers. The results indicate that the selected SO/EO ratio and copolymer block lengths were optimal for simultaneously achieving low critical micelle concentrations (cmc) values and large drug encapsulation ability. The amount of drug released from the polymeric micelles was larger at pH 7.4 than at acidic conditions, although still sustained over 1 day.
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Antifúngicos/administración & dosificación , Preparaciones de Acción Retardada/química , Griseofulvina/administración & dosificación , Micelas , Polietilenglicoles/química , Poliestirenos/química , Antifúngicos/química , Geles/química , Griseofulvina/química , Reología , SolubilidadRESUMEN
We have used pyrene fluorescence spectroscopy and isothermal titration calorimetry (ITC) to investigate the effect of hydrophobic-block length on values of the critical micelle concentration (cmc) for aqueous solutions of triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers (B(n)E(m)B(n), where m and n denote the respective block lengths) with hydrophobic block lengths in the range n=12-21. Combined with results from previous work on B(n)E(m)B(n) copolymers with shorter B blocks, plots of log(10)(cmc) (cmc in molar units and reduced to a common E-block length) against total number of B units (n(t)=n for diblock or n(t)=2n for triblock copolymers) display transitions in the slopes of the two plots, which indicate changes in the micellisation equilibrium. These occur at values of n(t)which can be assigned to the onset and completion of collapse of the hydrophobic B blocks, an effect not previously observed for reverse triblock copolymers. The results are compared with related data for diblock E(m)B(n) copolymers.
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Compuestos Epoxi/química , Polietilenglicoles/química , Calorimetría , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Espectrometría de FluorescenciaRESUMEN
In the present work, the formation and stabilization of gold nanoparticles in a one-pot water-based synthesis has been achieved in the presence of a four-arm, star-shaped polyoxyethyelene-polyoxypropylene (PEO-PPO) block copolymer, Tetronic T904, which acts as both reductant and stabilizer. The influence of several parameters such as copolymer and gold salt concentration, reaction temperature, and solution pH on both the size and shape of the resulting nanocrystals has been established. Low copolymer/gold salt molar ratios favor the formation of either triangular or hexagonal planar nanostructures due to a low reduction rate which turns the reaction into kinetic control. As the molar ratio increases, reduction becomes faster with the subsequent increase in the number of crystal seeds and, thus, the decrease in particle size. In addition, there is an increase in the reduction rate which causes the reduction reaction to be governed by thermodynamics, and consequently, spherical geometries are favored. A particle spherical shape can also be promoted as a consequence of the accumulation of block copolymer molecules on different crystallographic planes, homogenizing the metal surface structure and disabling the growth in different crystallographic directions. The same behavior was observed when the reaction temperature was raised. The size and shape of gold nanoparticles could also be controlled by varying the pH of the medium. As the pH becomes more acidic, protons prevent the oxyethylene part of the copolymer from the reduction of metal ions, and consequently, the number of nuclei decreases. This explains the overall increase in the particle size and the change in shape when the synthesis is carried out in acid medium. Finally, comparison with nanoparticles obtained in the presence of a structurally related linear block copolymer Pluronic P105, with a similar number of EO and PO units as T904, denoted an important incidence of the arrangement of PEO and PPO blocks on the reduction reaction rate and the size and shape of the resulting nanoparticles.