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1.
J Mater Chem B ; 12(31): 7577-7590, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38984432

RESUMEN

The development of new fluorescent probes as molecular sensors is a critical step for the understanding of molecular mechanisms. BODIPY-based probes offer versatility due to their high fluorescence quantum yields, photostability, and tunable absorption/emission wavelengths. Here, we report the synthesis and evaluation of a novel 7-azaindole-BODIPY derivative to probe hydrophobic proteins as well as protein misfolding and aggregation. In organic solvents, this compound shows two efficiently interconverting emissive excited states. In aqueous environments, it forms molecular aggregates with unique photophysical properties. The complex photophysics of the 7-azaindole-BODIPY derivative was explored for sensing applications. In the presence of albumin, the compound is stabilized in hydrophobic protein regions, significantly increasing its fluorescence emission intensity and lifetime. Similar effects occur in the presence of protein aggregates but not with other macromolecules like pepsin, DNA, Ficoll 40, and coconut oil. Fluorescence lifetime imaging microscopy (FLIM) and two-photon fluorescence microscopy on breast (MCF-7) and lung (A549) cancer cells incubated with this compound display longer fluorescence lifetimes and higher emission intensity under oxidative stress. Synchrotron FTIR micro spectroscopy confirmed that the photophysical changes observed were due to protein misfolding and aggregation caused by the oxidative stress. These findings demonstrate that this compound can serve as a fluorescent probe to monitor protein misfolding and aggregation triggered by oxidative stress.


Asunto(s)
Compuestos de Boro , Colorantes Fluorescentes , Estrés Oxidativo , Agregado de Proteínas , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Compuestos de Boro/química , Compuestos de Boro/síntesis química , Humanos , Indoles/química , Indoles/síntesis química , Imagen Óptica , Estructura Molecular , Microscopía Fluorescente
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124823, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39033609

RESUMEN

In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pKa values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (Ka = 4.10 × 106 M-1) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH0 = -54.49 kJ/mol; ΔS0 = -58.90 J K-1 mol-1) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed.


Asunto(s)
Alginatos , Bentonita , Nanocompuestos , Espectrometría de Fluorescencia , Humanos , Alginatos/química , Bentonita/química , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Nanocompuestos/química , Unión Proteica , Pteridinas/química , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Termodinámica
3.
Biomed Pharmacother ; 178: 117165, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059354

RESUMEN

Colorectal cancer (CRC) is the third most common cancer worldwide. Recent experiments suggest that CDK12 can be a good therapeutic target in CRC, and therefore, novel inhibitors targeting this protein are currently in preclinical development. Lipid-based formulations of chemical entities have demonstrated the ability to enhance activity while improving the safety profile. In the present work, we explore the antitumor activity of a new CDK12 inhibitor (CDK12-IN-E9, CDK12i) and its lipid-based formulation (LP-CDK12i) in CRC models, to increase efficacy. SW620, SW480 and HCT116 CRC cell lines were used to evaluate the inhibitor and the liposomal formulation using MTT proliferation assay, 3D invasion cultures, flow cytometry, Western blotting and immunofluorescence experiments. Free-cholesterol liposomal formulations of CDK12i (LP-CDK12i) were obtained by solvent injection method and fully characterized by size, shape, polydispersity, encapsulation efficiency, and release profile and stability assessments. LP-CDK12i induced a higher antiproliferative effect compared with CDK12i as a free agent. The IC50 value was lower across all cell lines tested, leading to a reduction in cell proliferation and the formation of 3D structures. Evaluation of apoptosis revealed an increase in cell death, while biochemical studies demonstrated modifications of apoptosis and DNA damage components. In conclusion, we confirm the role of targeting CDK12 for the treatment of CRC and describe, for the first time, a liposomal formulation of a CDK12i with higher antiproliferative activity compared with the free compound.


Asunto(s)
Antineoplásicos , Apoptosis , Proliferación Celular , Neoplasias Colorrectales , Quinasas Ciclina-Dependientes , Liposomas , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Proliferación Celular/efectos de los fármacos , Antineoplásicos/farmacología , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Quinasas Ciclina-Dependientes/metabolismo , Células HCT116 , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química
4.
J Colloid Interface Sci ; 674: 186-193, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38925064

RESUMEN

The effective measurement of temperature in living systems at the nano and microscopic scales continues to be a challenge to this day. Here, we study the use of 2-(anthracen-2-yl)-1,3-diisopropylguanidine, 1, as a nanothermometer based on fluorescence lifetime measurements and its bioimaging applications. In aqueous solution, 1 is shown in aggregated form and the equilibrium between the two main aggregate types (T-shaped and π-π) is highly sensitive to the temperature. The heating of the medium shifts the equilibrium toward the formation of highly emissive T-shaped aggregates. This species shows a high fluorescence emission and a long lifetime in comparison with the π-π aggregates and the freé monomer. A linear relationship between the fluorescence lifetime and the temperature both in aqueous solution and in a synthetic intracellular buffer was found. Fluorescence lifetime imaging microscopy (FLIM) also showed a linear relationship between lifetime and temperature with an excellent sensitivity in MCF7 breast cancer cells, which opens the door for its potential use as FLIM nanothermometer in the biomedical field.


Asunto(s)
Antracenos , Humanos , Antracenos/química , Células MCF-7 , Microscopía Fluorescente , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Termómetros , Fluorescencia , Temperatura , Imagen Óptica
5.
Inorg Chem ; 63(26): 12120-12132, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38873888

RESUMEN

Two series of boron derivatives with propiolamidinato ligands, [BPh2{C(C≡CAr)(NR)2}] (Ar = Ph, p-MeOPh, p-FPh, p-Me2NPh, or phen; R = iPr or p-tolyl), were synthesized and structurally characterized. The corresponding propiolamidine (or propargylamidine) proligands have been obtained through sustainable methods. One is the catalytic hydroalkynylation of diisopropylcarbodiimide with different terminal alkynes, using simple ZnEt2 as a precatalyst. Alternatively, to obtain propiolamidines with aromatic groups on the nitrogen atoms, the formation of lithiated derivatives of terminal alkynes by reaction with n-BuLi in air and at room temperature, and subsequent addition to the di-p-tolylcarbodiimide, under the same conditions and using 2-MeTHF as a sustainable solvent, has been used for the first time. After reaction with BPh3, the corresponding boron amidinates were obtained, which are emissive in the solution state. The influence of the different substituents introduced into the ligands on the photophysical properties of the boron compounds has been studied. One of the obtained compounds can be used as a ratiometric fluorescent pH sensor in the acidic range.

6.
J Inorg Biochem ; 253: 112486, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38266323

RESUMEN

The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of heteroscorpionate-based ruthenium derivatives was synthesized, characterized, and evaluated as an alternative to platinum therapy for breast cancer therapy. In vitro, the antitumoral activity of the novel derivatives was assessed in a series of breast cancer cell lines using UNICAM-1 and cisplatin as metallodrug control. Through this approach, a bimetallic heteroscorpionate-based metallodrug (RUSCO-2) was identified as the lead compound of the series with an IC50 value range as low as 3-5 µM. Notably, RUSCO-2 was found to be highly cytotoxic in TNBC cell lines, suggesting a mode of action independent of the receptor status of the cells. As a proof of concept and taking advantage of the luminescent properties of one of the complexes obtained, uptake was monitored in human breast cancer MCF7 cell lines by fluorescence lifetime imaging microscopy (FLIM) to reveal that the compound is evenly distributed in the cytoplasm and that the incorporation of the heteroscorpionate ligand protects it from aqueous processes, conversion in another entity, or the loss of the chloride group. Finally, ROS studies were conducted, lipophilicity was estimated, the chloride/water exchange was studied, and stability studies in simulated biological media were carried out to propose structure-activity relationships.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Complejos de Coordinación , Rutenio , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Rutenio/farmacología , Rutenio/uso terapéutico , Ligandos , Cloruros , Células MCF-7 , Línea Celular Tumoral
7.
Int J Mol Sci ; 24(18)2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37762123

RESUMEN

The modular synthesis of the guanidine core by guanylation reactions using commercially available ZnEt2 as a catalyst has been exploited as a tool for the rapid development of antitumoral guanidine candidates. Therefore, a series of phenyl-guanidines were straightforwardly obtained in very high yields. From the in vitro assessment of the antitumoral activity of such structurally diverse guanidines, the guanidine termed ACB3 has been identified as the lead compound of the series. Several biological assays, an estimation of AMDE values, and an uptake study using Fluorescence Lifetime Imaging Microscopy were conducted to gain insight into the mechanism of action. Cell death apoptosis, induction of cell cycle arrest, and reduction in cell adhesion and colony formation have been demonstrated for the lead compound in the series. In this work, and as a proof of concept, we discuss the potential of the catalytic guanylation reactions for high-throughput testing and the rational design of guanidine-based cancer therapeutic agents.


Asunto(s)
Guanidinas , Neoplasias , Humanos , Guanidina , Guanidinas/farmacología , Apoptosis , Muerte Celular , Neoplasias/tratamiento farmacológico
8.
ACS Appl Mater Interfaces ; 15(38): 44786-44795, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37699547

RESUMEN

AIEgens have emerged as a promising alternative to molecular rotors in bioimaging applications. However, transferring the concept of aggregation-induced emission (AIE) from solution to living systems remains a challenge. Given the highly heterogeneous nature and the compartmentalization of the cell, different approaches are needed to control the self-assembly within the crowded intricate cellular environment. Herein, we report for the first time the self-assembly mechanism of an anthracene-guanidine derivative (AG) forming the rare and highly emissive T-shaped dimer in breast cancer cell lines as a proof of concept. This process is highly sensitive to the local environment in terms of polarity, viscosity, and/or water quantity that should enable the use of the AG as a fluorescence lifetime imaging biosensor for intracellular imaging of cellular structures and the monitoring of intracellular state parameters. Different populations of the monomer and T-shaped and π-π dimers were observed in the cell membrane, cytoplasm, and nucleoplasm, related to the local viscosity and presence of water. The T-shaped dimer is formed preferentially in the nucleus because of the higher density and viscosity compared to the cytoplasm. The present results should serve as a precursor for the development of new design strategies for molecular systems for a wide range of applications such as cell viscosity, density, or temperature sensing and imaging.


Asunto(s)
Antracenos , Imagen Óptica , Citoplasma , Membrana Celular , Polímeros , Agua
9.
Mol Pharm ; 20(3): 1631-1642, 2023 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-36812406

RESUMEN

The binding processes of two Polo-like kinase inhibitors, RO3280 and GSK461364, to the human serum albumin (HSA) protein as well as the protonation equilibria of both compounds have been studied combining absorbance and fluorescence spectroscopy experiments together with density functional theory calculations. We found that the charge states of RO3280 and GSK461364 are +2 and +1, respectively, at the physiological pH. Nevertheless, RO3280 binds to HSA in the charge state +1 prior to a deprotonation pre-equilibrium. Binding constants to site I of HSA of 2.23 × 106 and 8.80 × 104 M-1 were determined for RO3280 and GSK461364, respectively, at 310 K. The binding processes of RO3280 and GSK461364 to HSA are entropy- and enthalpy-driven, respectively. The positive enthalpy found for the RO3280-HSA complex formation could be related to a proton pre-equilibrium of RO3280.


Asunto(s)
Albúmina Sérica Humana , Albúmina Sérica , Humanos , Albúmina Sérica/metabolismo , Unión Proteica , Albúmina Sérica Humana/metabolismo , Termodinámica , Espectrometría de Fluorescencia , Sitios de Unión
10.
J Mater Chem B ; 11(2): 316-324, 2023 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-36353924

RESUMEN

Population growth, depletion of world resources and persistent toxic chemical production underline the need to seek new smart materials from inexpensive, biodegradable, and renewable feedstocks. Hence, "metal-free" ring-opening copolymerization to convert biomass carvone-based monomers into non-conventional luminescent biopolymers is considered a sustainable approach to achieve these goals. The non-conventional emission was studied in terms of steady-state and time-resolved spectroscopy in order to unravel the structure-properties for different carvone-based copolymers. The results highlighted the importance of the final copolymer folding structure as well as its environment in luminescent behavior (cluster-triggered emission). In all cases, their luminescent behavior is sensitive to small temperature fluctuations (where the minimum detected temperature is Tm ∼ 2 °C and relative sensitivity is Sr ∼ 6% °C) even at the microscopic scale, which endows these materials a great potential as thermosensitive smart polymers for photothermal imaging.


Asunto(s)
Luminiscencia , Polímeros , Polímeros/química , Biomasa , Monoterpenos Ciclohexánicos
11.
Antioxidants (Basel) ; 11(10)2022 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-36290711

RESUMEN

The advent of nanotechnology in the field of animal reproduction has led to the development of safer and more efficient therapies. The use of nanotechnology allows us to avoid the detrimental effects of certain traditional antioxidants, such as Vitamin E. Its hydrophobic nature makes mandatory the use of organic solvents, which are toxic to sperm cells. This study aims to evaluate the efficiency of vitamin E nanoemulsions (NE) on ram (Ovis aries) spermatozoa. For this purpose, the effect of three NE concentrations (6, 12, and 24 mM) were assessed on sperm of 10 mature rams of the Manchega breed. Sperm samples were collected by artificial vagina, pooled, and diluted in Bovine Gamete Medium. The samples were stored at 37 °C and assessed at 0, 4, 8, and 24 h under oxidative stress conditions (100 µM Fe2+/ascorbate). Motility (CASA), viability (YO-PRO/IP), acrosomal integrity (PNA-FITC/IP), mitochondrial membrane potential (Mitotracker Deep Red 633), lipoperoxidation (C11 BODIPY 581/591), intracellular reactive oxygen species (ROS) production and DNA status (SCSA®®) were assessed. A linear mixed-effects models were used to analyze the effects of time, NE, and oxidant (fixed factors) on sperm parameters, and a random effect on the male was also included in the model with Tukey's post hoc test. Protection of ram spermatozoa with NE resulted in a more vigorous motility under oxidative stress conditions with respect Control and Free vitamin E, while preventing the deleterious effects of oxidative stress coming from the production of free radicals and lipid peroxidation. These results ascertain the high relevance of the use of delivery systems for sperm physiology preservation in the context of assisted reproduction techniques.

12.
Cancers (Basel) ; 14(18)2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-36139634

RESUMEN

BRCA1/2 protein-deficient or mutated cancers comprise a group of aggressive malignancies. Although PARPis have shown considerably efficacy in their treatment, the widespread use of these agents in clinical practice is restricted by various factors, including the development of acquired resistance due to the presence of compensatory pathways. BETis can completely disrupt the HR pathway by repressing the expression of BRCA1 and could be aimed at generation combination regimes to overcome PARPi resistance and enhance PARPi efficacy. Due to the poor pharmacokinetic profile and short half-life, the first-in-class BETi JQ1 was loaded into newly developed nanocarrier formulations to improve the effectivity of olaparib for the treatment of BRCAness cancers. First, polylactide polymeric nanoparticles were generated by double emulsion. Moreover, liposomes were prepared by ethanol injection and evaporation solvent method. JQ1-loaded drug delivery systems display optimal hydrodynamic radii between 60 and 120 nm, with a very low polydispersity index (PdI), and encapsulation efficiencies of 92 and 16% for lipid- and polymeric-based formulations, respectively. Formulations show high stability and sustained release. We confirmed that all assayed JQ1 formulations improved antiproliferative activity compared to the free JQ1 in models of ovarian and breast cancers. In addition, synergistic interaction between JQ1 and JQ1-loaded nanocarriers and olaparib evidenced the ability of encapsulated JQ1 to enhance antitumoral activity of PARPis.

13.
Gels ; 8(9)2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36135306

RESUMEN

Gelatin is a popular biopolymer for biomedical applications due to its harmless impact with a negligible inflammatory response in the host organism. Gelatin interacts with soluble molecules in aqueous media as ionic counterparts such as ionic liquids (ILs) to be used as cosolvents to generate the so-called Ionogels. The perfluorinated IL (FIL), 1-ethyl-3-methylpyridinium perfluorobutanesulfonate, has been selected as co-hydrosolvent for fish gelatin due to its low cytotoxicity and hydrophobicity aprotic polar structure to improve the drug aqueous solubility. A series of FIL/water emulsions with different FIL content and their corresponding shark gelatin/FIL Ionogel has been designed to enhance the drug solubility whilst retaining the mechanical structure and their nanostructure was probed by simultaneous SAXS/WAXS, FTIR and Raman spectroscopy, DSC and rheological experiments. Likewise, the FIL assisted the solubility of the antitumoural Doxorubicin whilst retaining the performing mechanical properties of the drug delivery system network for the drug storage as well as the local administration by a syringe. In addition, the different controlled release mechanisms of two different antitumoral such as Doxorubicin and Mithramycin from two different Ionogels formulations were compared to previous gelatin hydrogels which proved the key structure correlation required to attain specific therapeutic dosages.

14.
Pharmaceutics ; 14(8)2022 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-36015299

RESUMEN

The incessant developments in the pharmaceutical and biomedical fields, particularly, customised solutions for specific diseases with targeted therapeutic treatments, require the design of multicomponent materials with multifunctional capabilities. Biodegradable polymers offer a variety of tailored physicochemical properties minimising health adverse side effects at a low price and weight, which are ideal to design matrices for hybrid materials. PLAs emerge as an ideal candidate to develop novel materials as are endowed withcombined ambivalent performance parameters. The state-of-the-art of use of PLA-based materials aimed at pharmaceutical and biomedical applications is reviewed, with an emphasis on the correlation between the synthesis and the processing conditions that define the nanostructure generated, with the final performance studies typically conducted with either therapeutic agents by in vitro and/or in vivo experiments or biomedical devices.

15.
J Photochem Photobiol B ; 232: 112477, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35644070

RESUMEN

In the present work, the interactions of the novel kinase inhibitors BI-2536, Volasetib (BI-6727) and Ro-3280 with the pharmacological target PLK1 have been studied by fluorescence spectroscopy and molecular dynamics calculations. High Stern-Volmer constants were found in fluorescence experiments suggesting the formation of stable protein-ligand complexes. In addition, it was observed that the binding constant between BI-2536 and PLK1 increases about 100-fold in presence of the phosphopeptide Cdc25C-p that docks to the polo box domain of the protein and releases the kinase domain. All the determined binding constants are higher for the kinase inhibitors than for their competitor for the active center (ATP) being BI-2536 and Volasertib the inhibitors that showed more affinity for PLK1. Calculated binding free energies confirmed the higher affinity of PLK1 for BI-2536 and Volasertib than for ATP. The higher affinity of the inhibitors to PLK1 compared to ATP was mainly attributed to stronger van der Waals interactions. Results may help with the challenge of designing and developing new kinase inhibitors more effective in clinical cancer therapy.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinasas , Adenosina Trifosfato , Proteínas de Ciclo Celular/metabolismo , Inhibidores de Proteínas Quinasas/química , Proteínas Proto-Oncogénicas/metabolismo , Pteridinas
16.
Pharmaceutics ; 14(6)2022 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-35745711

RESUMEN

A series of bionanocomposites composed of shark gelatin hydrogels and PLA nanoparticles featuring different nanostructures were designed to generate multifunctional drug delivery systems with tailored release rates required for personalized treatment approaches. The global conception of the systems was considered from the desired customization of the drug release while featuring the viscoelastic properties needed for their ease of storage and posterior local administration as well as their biocompatibility and cell growth capability for the successful administration at the biomolecular level. The hydrogel matrix offers the support to develop a direct thermal method to convert the typical kinetic trapped nanostructures afforded by the formulation method whilst avoiding the detrimental nanoparticle agglomeration that diminishes their therapeutic effect. The nanoparticles generated were successfully formulated with two different antitumoral compounds (doxorubicin and dasatinib) possessing different structures to prove the loading versatility of the drug delivery system. The bionanocomposites were characterized by several techniques (SEM, DLS, RAMAN, DSC, SAXS/WAXS and rheology) as well as their reversible sol-gel transition upon thermal treatment that occurs during the drug delivery system preparation and the thermal annealing step. In addition, the local applicability of the drug delivery system was assessed by the so-called "syringe test" to validate both the storage capability and its flow properties at simulated physiological conditions. Finally, the drug release profiles of the doxorubicin from both the PLA nanoparticles or the bionanocomposites were analyzed and correlated to the nanostructure of the drug delivery system.

17.
Gels ; 8(4)2022 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-35448138

RESUMEN

The skin of yellowfin tuna is one of the fishery industry solid residues with the greatest potential to add extra value to its circular economy that remains yet unexploited. Particularly, the high collagen content of fish skin allows generating gelatin by hydrolysis, which is ideal for forming hydrogels due to its biocompatibility and gelling capability. Hydrogels have been used as drug carriers for local administration due to their mechanical properties and drug loading capacity. Herein, novel tuna gelatin hydrogels were designed as drug vehicles with two structurally different antitumoral model compounds such as Doxorubicin and Crocin to be administrated locally in tissues with complex human anatomies after surgical resection. The characterization by gel permeation chromatography (GPC) of purified gelatin confirmed their heterogeneity composition, exhibiting three major bands that correspond to the ß and α chains along with high molecular weight species. In addition, the Fourier Transform Infrared (FT-IR) spectra of gelatin probed the secondary structure of the gelatin showing the simultaneous existence of α helix, ß sheet, and random coil structures. Morphological studies at different length scales were performed by a multi-technique approach using SAXS/WAXS, AFM and cryo-SEM that revealed the porous network formed by the interaction of gelatin planar aggregates. In addition, the sol-gel transition, as well as the gelation point and the hydrogel strength, were studied using dynamic rheology and differential scanning calorimetry. Likewise, the loading and release profiles followed by UV-visible spectroscopy indicated that the novel gelatin hydrogels improve the drug release of Doxorubicin and Crocin in a sustained fashion, indicating the structure-function importance in the material composition.

18.
Polymers (Basel) ; 14(2)2022 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-35054639

RESUMEN

Stereo-diblock copolymers of high molecular weight polylactide (PLA) were synthetized by the one pot-sequential addition method assisted by a heteroscorpionate catalyst without the need of a co-initiator. The alkyl zinc organometallic heteroscorpionate derivative (Zn(Et)(κ3-bpzteH)] (bpzteH = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1-para-tolylethoxide) proved to assist in the mechanism of reaction following a coordination-insertion process. Kinetic studies along with the linear correlation between monomer and number average molecular weight (Mn) conversion, and the narrow polydispersities supported the truly living polymerization character of the initiator, whereas matrix-assisted laser desorption/Ionization-time of flight (MALDI-TOF) studies showed a very low order of transesterification. The high stereo-control attained for the afforded high molecular weight derivatives was revealed by homonuclear decoupled 1H NMR spectra and polarimetry measurements. The nanostructure of the PLA derivatives was studied by both wide-angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC) and the stereocomplex phase of the PLA stereo-diblock copolymers was successfully identified.

19.
ACS Appl Mater Interfaces ; 14(2): 2578-2586, 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-35001616

RESUMEN

The use of two nanoparticles for quantitative pH measurements in live cells by means of fluorescence lifetime imaging microscopy (FLIM) is investigated here. These nanoparticles are based on CdSe/ZnS quantum dots (QDs), functionalized with N-acetylcysteine (CdSe/ZnS-A) and with a small peptide containing D-penicillamine and histidine (CdSe/ZnS-PH). CdSe/ZnS-A has tendency to aggregate and nonlinear pH sensitivity in a complex medium containing salts and macromolecules. On the contrary, CdSe/ZnS-PH shows chemical stability, low toxicity, efficient uptake in C3H10T1/2 cells, and good performance as an FLIM probe. CdSe/ZnS-PH also has key advantages over a recently reported probe based on a CdSe/ZnS QD functionalized with D-penicillamine (longer lifetimes and higher pH-sensitivity). A pH(±2σ) of 6.97 ± 0.14 was determined for C3H10T1/2 cells by FLIM employing this nanoprobe. In addition, the fluorescence lifetime signal remains nearly constant for C3H10T1/2 cells treated with CdSe/ZnS-PH for 24 h. These results show the promising applications of this nanoprobe to monitor the intracellular pH and cell state employing the FLIM technique.


Asunto(s)
Materiales Biocompatibles/química , Colorantes Fluorescentes/química , Imagen Óptica , Puntos Cuánticos/química , Animales , Células Cultivadas , Concentración de Iones de Hidrógeno , Ensayo de Materiales , Ratones , Microscopía Fluorescente , Estructura Molecular
20.
Cuad. psicol. deporte ; 22(1): 57-66, ene. - abr. 2022. tab
Artículo en Español | IBECS | ID: ibc-208958

RESUMEN

El presente estudio tuvo como objetivo analizar la relación entre el conflicto intra-grupo y el rendimiento percibido a final de temporada, y examinar como actúa la eficacia colectiva como variable mediadora en esta asociación. Participaron 420 jugadores semi-profesionales y amateurs (M = 22,40; DT = 4,71) de baloncesto, balonmano, fútbol y voleibol. Los resultados mostraron que el conflicto intra-grupo (tarea y social) se relacionó negativamente con el rendimiento percibido del equipo, y que la eficacia colectiva mostró resultados significativos actuando como mediadora entre la relación de el conflicto intra-grupo (tarea y social) y el rendimiento percibido del equipo. Por lo tanto, es importante destacar que los conflictos intra-grupo parecen empeorar las percepciones sobre el rendimiento grupal y que la eficacia colectiva puede suavizar esta relación negativa, consiguiendo un aumento en el la percepción de los jugadores sobre el rendimiento del equipo a final de temporada. (AU)


The present study aimed to analyze the relationship between intra-group conflict and team perceived performance at the end of the season, and to examine the mediating effect of collective efficacy on this relationship. 420 semi-professional and amateur players (M = 22,40; SD = 4,71) of basketball, handball, soccer and volleyball participated. The results showed that intra-group conflict (task and social) was negatively related to team performance and collective efficacy showed significant results acting as a mediator between the relationship of intra-group conflict (task and social) and team perceived performance. Therefore, it is important to highlight that intra-group conflict seems to worsen the collective functioning and that collective efficacy can soften this negative relationship, achieving an increase in team performance at the end of the season. (AU)


O presente estudo teve como objetivo analisar a relação entre conflito intra-grupo e desempenho percebido no final da temporada, e examinar como a eficácia coletiva atua como uma variável mediadora nesta associação. Participaram 420 jogadores semiprofissionais e amadores (M = 22,40; DT = 4,71) de basquete, handebol, futebol e voleibol. Os resultados mostraram que o conflito intra-grupo (trabalho de casa e social) estava negativamente relacionado ao desempenho percebido da equipe e que a eficácia coletiva apresentou resultados significativos atuando como mediador entre a relação do conflito intra-grupo (trabalho de casa e social) e o desempenho percebido da equipe. Portanto, é importante destacar que o conflito intra-grupo parece agravar o funcionamento coletivo da equipe e que a eficácia coletiva pode amenizar essa relação negativa, conseguindo um aumento na percepção do desempenho da equipe no final da temporada. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Deportes/psicología , Equipo Deportivo , Rendimiento Atlético , Encuestas y Cuestionarios , España , 28599
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