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1.
Phys Chem Chem Phys ; 16(6): 2378-83, 2014 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-24352700

RESUMEN

We study the electron spin decoherence of encapsulated atomic hydrogen in octasilsesquioxane cages induced by the (1)H and (29)Si nuclear spin bath. By applying the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence we significantly suppress the low-frequency noise due to nuclear spin flip-flops up to the point where a maximum T2 = 56 µs is observed. Moreover, dynamical decoupling with the CPMG sequence reveals the existence of two other sources of decoherence: first, a classical magnetic field noise imposed by the (1)H nuclear spins of the cage organic substituents, which can be described by a virtual fluctuating magnetic field with the proton Larmor frequency, and second, decoherence due to anisotropic hyperfine coupling between the electron and the inner (29)Si spins of the cage.

2.
J Lipid Res ; 54(1): 164-76, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23110818

RESUMEN

Lipoprotein glomerulopathy (LPG) is a dominant inherited kidney disorder characterized by lipoprotein thrombi in glomerular capillaries. Single-amino-acid mutations in apoE have been associated with the development of the disease, although the mechanism is unknown. In an effort to gain mechanistic insight linking the presence of such mutations and the development of LPG, we evaluated the effects of three of the most common apoE3 variants associated with this disease, namely R145P(Sendai), R147P(Chicago), and R158P(Osaka or Kurashiki), on the structural and conformational integrity of the protein. All three variants were found to have significantly reduced helical content, to expose a larger portion of hydrophobic surface to the solvent, and to be significantly thermodynamically destabilized, often lacking functionally relevant unfolding intermediates. Furthermore, all variants were aggregation prone and had enhanced sensitivity to protease digestion. Finally, although the variants were able to form discoidal lipoprotein particles, discrete subpopulations of poorly formed or aberrant particles were evident. Furthermore, these lipoprotein particles were thermodynamically destabilized and aggregation prone. Overall, our data suggest that these mutations induce a generalized unfolding of the N-terminal domain of apoE3 toward a molten-globule-like structure. ApoE3 N-terminal domain unfolding due to mutation may constitute a common mechanism underlying the protein's association with the pathogenesis of LPG.


Asunto(s)
Apolipoproteína E3/química , Apolipoproteína E3/metabolismo , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Glomérulos Renales/metabolismo , Lipoproteínas/metabolismo , Mutación , Apolipoproteína E3/genética , HDL-Colesterol/química , HDL-Colesterol/metabolismo , Dimiristoilfosfatidilcolina/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Enfermedades Renales/patología , Modelos Moleculares , Péptido Hidrolasas/metabolismo , Multimerización de Proteína , Estabilidad Proteica , Estructura Cuaternaria de Proteína , Estructura Secundaria de Proteína , Termodinámica
3.
Materials (Basel) ; 15(11)2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35683211

RESUMEN

This paper reports developing an innovative method of anticorrosion protection based on organically modified silica (ORMOSIL) enriched with CeO2 ceramic nanocontainers loaded with 5-amino-1, 3, 4-thiadiazole-2-thiol (5-ATDT) on hot-dip galvanized zinc (HDG) steel used to strengthen cement in concrete. The chemistry of ORMOSIL coatings and the production of CeO2 ceramic nanocontainers are described in detail for reproduction by other researchers. The anticorrosion properties of these novel coatings were investigated through frequency response analysis (FRA). As a result, the coatings HDG-ORMOSIL + CeO2 (5-ATDT) were better than the samples of HDG steel, HDG-ORMOSIL, and HDG-ORMOSIL + CeO2 (EMPTY) by a factor of 1033.60, 109.21, and 7.76 in terms of anticorrosion protection, respectively.

4.
J Nanosci Nanotechnol ; 10(9): 5912-20, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21133128

RESUMEN

Titania nanocontainers were synthesized through a two-step process and then loaded with 8-hydroxyquinoline (8-HQ) and p-toluenesulfonic acid (p-TSA). The size of the containers was 242 +/- 10 nm as determined by Scanning Electron Microscopy (SEM). X-Ray Diffraction Analysis (XRD) showed that the titania nanocontainers consist of anatase and rutile crystalline phases. The presence of 8-HQ and p-TSA in the nanocontainers was confirmed with Fourier Transform Infrared Spectroscopy (FT-IR). The loading of the inhibitors in the nanocontainers was estimated with Thermo Gravimetric Analysis (TGA). The loading amount of 8-HQ is 3.56% w/w and that of p-TSA is 6.13%. Based on the size of the nanocontainers and the assumption that they are not broken, the amount of approximately with 2.83 x 10(6) molecules of 8-HQ and 3.86 x 10(6) molecules of p-TSA per nanocontainer was estimated. Furthermore, release studies of 8-HQ and p-TSA in a corrosive environment were studied by potentiodynamic measurements showing that the inhibitors are released from the nanocontainers, suppressing the corrosion activities. SEM and Dynamic Light Scattering (DLS) measurements confirmed that the nanocontainers are not agglomerated and keep their shape after suspension in 0.5 M NaCI solution for more than 72 hours.

5.
Phys Med ; 71: 39-52, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32088564

RESUMEN

PURPOSE: The purpose of this study is to employ magnetic fluid hyperthermia simulations in the precise computation of Specific Absorption Rate functions -SAR(T)-, and in the evaluation of the predictive capacity of different SAR calculation methods. METHODS: Magnetic fluid hyperthermia experiments were carried out using magnetite-based nanofluids. The respective SAR values were estimated through four different calculation methods including the initial slope method, the Box-Lucas method, the corrected slope method and the incremental analysis method (INCAM). A novel numerical model combining the heat transfer equations and the Navier-Stokes equations was developed to reproduce the experimental heating process. To address variations in heating efficiency with temperature, the expression of the power dissipation as a Gaussian function of temperature was introduced and the Levenberg-Marquardt optimization algorithm was employed to compute the function parameters and determine the function's effective branch within each measurement's temperature range. The power dissipation function was then reduced to the respective SAR function. RESULTS: The INCAM exhibited the lowest relative errors ranging between 0.62 and 15.03% with respect to the simulations. SAR(T) functions exhibited significant variations, up to 45%, within the MFH-relevant temperature range. CONCLUSIONS: The examined calculation methods are not suitable to accurately quantify the heating efficiency of a magnetic fluid. Numerical models can be exploited to effectively compute SAR(T) and contribute to the development of robust hyperthermia treatment planning applications.


Asunto(s)
Hipertermia Inducida/métodos , Magnetismo , Algoritmos , Calorimetría , Simulación por Computador , Calor , Humanos , Modelos Lineales , Nanopartículas de Magnetita , Distribución Normal , Reproducibilidad de los Resultados
6.
J Chem Phys ; 129(15): 154502, 2008 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-19045204

RESUMEN

(100-x) mol % B(2)O(3) x mol % Me(2)O (Me = Li,Na,K) glasses, exposed to gamma-(60)Co irradiation to produce paramagnetic states, were characterized by W-band (95 GHz) pulse electron-nuclear double resonance (ENDOR) spectroscopy in order to characterize local structures occurring in the range of compositions between x=16 and x=25 at which the "boron oxide" anomaly occurs. The high resolution of nuclear frequencies allowed resolving the (7)Li and (11)B ENDOR lines. In the samples with x=16 and x=20 glasses, (11)B hyperfine couplings of 16, 24, and 36 MHz were observed and attributed to the tetraborate, triborate, and boron oxygen hole center (BOHC) structures, respectively. The x=25 samples showed hyperfine couplings of 15 MHz for the tetraborate and 36 MHz for BOHC. Density functional theory (DFT) calculations predicted for these structures negative hyperfine couplings, which were confirmed by W-band ENDOR. This suggests that a spin polarization mechanism accounts for the negative hyperfine structure splitting.

7.
Sci Rep ; 8(1): 14704, 2018 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-30279462

RESUMEN

Nanoscale drug delivery systems represent a promising strategy to treat cancer and to overcome the side effects of chemotherapy. In particular, hollow polymeric nanocontainers have attracted great interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of stimuli-responsive materials capable of responding to the biochemical alterations of the tumour microenvironment. Here are reported the synthesis, characterization and in vitro evaluation of a three-stimuli-sensitive hollow nanocontainer consisting of three different shells, each one sensitive to a specific tumoral stimulus: in order pH, temperature and reducing environment. To test its properties, daunorubicin was used as a model drug, for which the nanocontainers exhibited excellent encapsulation ability. The in vitro drug release behaviour was studied under different conditions, where the system proved capable of responding to the selected tumoral stimuli by releasing a larger amount of drug than in physiological environment. The hollow system itself showed negligible cytotoxicity but the loaded nanocontainers and free drug showed identical cytotoxicity and intracellular localization. Therefore, this formulation can be considered as a promising platform to develop an injectable delivery system capable of improving systematic toxicity without affecting or reducing the activity of the encapsulated drug.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Nanoestructuras/química , Neoplasias/tratamiento farmacológico , Antibióticos Antineoplásicos/farmacocinética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Daunorrubicina/administración & dosificación , Daunorrubicina/farmacocinética , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/farmacocinética , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Polímeros/síntesis química , Temperatura , Microambiente Tumoral/efectos de los fármacos
8.
Free Radic Res ; 51(5): 470-482, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28463089

RESUMEN

5',8-Cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo-2'-deoxyguanosine (cdG) in their two diastereomeric forms, 5'S and 5'R, are tandem lesions produced by the attack of hydroxyl radicals to the purine moieties of DNA. Their formation has been found to challenge the cells' repair machinery, initiating the nucleotide excision repair (NER) for restoring the genome integrity. The involvement of oxidatively induced DNA damage in carcinogenesis and the reduced capacity of some cancer cell lines to repair oxidised DNA base lesions, intrigued us to investigate the implication of these lesions in breast cancer, the most frequently occurring cancer in women. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), we measured the levels of diastereomeric cdA's and cdG's in estrogen receptor-alpha positive (ER-α) MCF-7 and triple negative MDA-MB-231 breast cancer cell lines before and after exposure to two different conditions: ionising radiations and hydrogen peroxide, followed by an interval period to allow DNA repair. An increase at the measured levels of all four lesions, i.e. 5'S-cdA, 5'R-cdA, 5'S-cdG and 5'R-cdG, was observed either after γ-irradiation (5 Gy dose) or hydrogen peroxide treatment (300 µM) compared to the untreated cells (control), independently from the length of the interval period for repair. For comparison reasons, we also measured the levels of 8-oxo-2'-deoxyadenosine (8-oxo-dA), a well-known oxidatively induced DNA damage lesion and base excision repair (BER) substrate. The collected data indicate that MCF-7 and MDA-MB-231 breast cancer cells are highly susceptible to radiation-induced DNA damage, being mainly defective in the repair of these lesions.


Asunto(s)
Daño del ADN , Células Epiteliales/metabolismo , Estrés Oxidativo , Neoplasias de la Mama , Desoxiadenosinas/genética , Desoxiadenosinas/metabolismo , Femenino , Humanos , Células MCF-7 , Glándulas Mamarias Humanas/patología , Especies Reactivas de Oxígeno/metabolismo
9.
Mater Sci Eng C Mater Biol Appl ; 79: 605-612, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28629059

RESUMEN

Nanostructured delivery and diagnostic systems that induces specific targeting properties by exploiting the local physicochemical tumour characteristics will be evaluated is the present work. It is well known that cancer cells have specific physicochemical characteristics, which can be taken into consideration for the design of a broad spectrum of drug delivery systems (DDS). Some of those characteristics including the different temperature environment their susceptibility when temperature ranges between 40 and 43°C where cell apoptosis is induced, the intra- and extra-cellular pH which varies from 6.0 to 6.8, for cancer cells, and 6.5 to 7.4 for normal cells respectively, (lysosomes acidic pH ranges 4-5). Additional significant factors are the overexpressed receptors on the tumour surface. Loading and release studies were carried out by using the anthracycline drug Doxorubicin and their cytotoxicity was evaluated by using the MTT assay in healthy and diseased cell lines. The highlight of this work is the in vitro and in vivo studies which were performed in order to evaluate different nanostructures as for their biodistribution, pharmacokinetic and toxicity per se.


Asunto(s)
Nanoestructuras , Antibióticos Antineoplásicos , Doxorrubicina , Sistemas de Liberación de Medicamentos , Humanos , Distribución Tisular
10.
Colloids Surf B Biointerfaces ; 148: 95-103, 2016 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-27591575

RESUMEN

A versatile drug delivery carrier that responds to external stimuli was synthesized via the emulsion polymerization process. This simple two-step process was carried out by using Poly (Methyl Methacrylate) as a soft template and a series of monomers, with desired properties, as coating monomers. It is noteworthy that during shell fabrication (2nd step) an inner cavity is created inside the nanocontainers that can be used as a host for small drug molecules. The thermo-, pH- and redox sensitive monomers used in the coating procedure were Dimethyl Amino Ethyl Methacrylate (DMAEMA), Acrylic Acid (AA) and N,N'-(disulfanediylbis(ethane-2,1-diyl))bis(2-methylacrylamide) (Disulfide or DS), respectively. It has to be noted that DMAEMA is also pH- sensitive and acts synergistically with AA. The surface of the multi-stimuli nanocontainers was functionalized with magnetite nanoparticles in order to induce an alternating magnetic field (AMF) sensitivity. By using AMF in various strenghts and frequencies, the temperature of the final multi-stimuli nanocontainers (Q-NCs) can be increased in a controlled manner resulting in the Hyperthermia phenomenon. Loading and release studies were carried out using the anthracycline drug, Doxorubicin, aiming at the confirmation of the release mechanism.


Asunto(s)
Nanoestructuras , Neoplasias/fisiopatología , Humanos , Microscopía Electrónica de Rastreo , Espectrometría Raman
11.
Macromol Biosci ; 14(1): 131-41, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24106236

RESUMEN

Magnetic nanodevices based on poly[(methacrylic acid)-co-(N-isopropylacrylamide)] [P(MAA-co-NIPAAm)] are prepared and used as drug delivery systems employing daunorubicin (DNR) as a model drug. The magnetic nanocontainers exploit the pH, temperature, and magnetic response of the polymeric shell constituents and magnetic nanoparticles, respectively, for controlled pH, temperature and alternating magnetic field triggered drug release. The in vitro cytotoxicity of both DNR-loaded and empty nanocontainers is examined on MCF-7 breast cancer cells along with the intracellular distribution of DNR. The results show that the DNR-loaded nanocontainers have an anti-tumor effect comparable to the free drug. The current observations provide important information for potent drug delivery and release systems.


Asunto(s)
Acrilamidas/química , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/administración & dosificación , Nanopartículas/química , Ácidos Polimetacrílicos/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Daunorrubicina/administración & dosificación , Femenino , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7/efectos de los fármacos , Fenómenos Magnéticos , Microscopía Confocal , Temperatura
12.
J Colloid Interface Sci ; 435: 171-81, 2014 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-25261841

RESUMEN

HYPOTHESIS: Conventional chemotherapy drugs such as anthracyclines show no specific activity. They destroy cancer cells but also and the healthy ones, and for that reason exhibit high toxicity. In order to alleviate the toxic effects of chemotherapeutic drugs, the administration dose is being minimized, while their reactivity against tumor cells is lessened. This problem can be overcome or at least reduced by using nanoscale drug delivery systems to target the pathogenic area. The present work deals with the synthesis, characterization and biological evaluation of multi-responsive hollow microspheres coated with Hydroxypropyl Cellulose (HPC)-a biocompatible and thermosensitive polysaccharide-conjugated with folic acid as well promising drug vehicles for targeted cancer therapy. EXPERIMENTS: The synthetic route consists of two steps. In the first step, a single layer of sensitive copolymers is ((Methacrylic acid (MAA), N-(2-Hydroxypropyl) methacrylamide (HPMA) and N,N'-(disulfanediylbis(ethane-2,1-diyl))bis(2-methylacrylamide) (DSBMA)) fabricated on a sacrificial template of SiO2 and in the second step, an additional layer of the folic acid modified HPC coat the microspheres' surface. The layers fabrication is performed through a combination of distillation precipitation co-polymerization and chemical deposition method. The loading capacity (% LC) and encapsulation efficiency (% EE) percentages of the chemotherapeutic agent daunorubicin (DNR) in the fabricated microspheres were calculated through the standard curve methodology. In addition, the releasing properties of the resulting spheres are investigated, using the above mentioned methodology. It is worth mentioning that, spheres release the entrapped drug under combined conditions such acidic and reductive environment along with conventional hyperthermia. Cytotoxic activity of the synthesized spheres was investigated by using the well-established method of MTT assay in MCF-7 (breast cancer), HeLa (cervical cancer) and HEK 293 (Human Embryonic Kidney healthy cells) cell lines. Confocal and fluorescence microscopy were used to confirm the in vitro targeted ability of folic acid modified drug loaded microspheres in HeLa, to that overexpress folate receptors, MCF-7 and 3T3 cells, as negative folate cell substrate. Finally, radiolabelling of the spheres is performed, with a gamma emitting radionuclide ((99m)Tc), to assess their in vivo profile by means of scintigraphic imaging and biodistribution studies. FINDINGS: Hollow spheres release the encapsulated drug under acidic environment, conventional hyperthermia or in the presence of glutathione (reductive environment). The ability of modified drug carriers to target the HeLa cells, was confirmed by confocal and fluorescence microscopy. The resulting spheres are observed to be promising drug-carriers for cancer treatment due to their releasing properties under tumor's environment and high concentration in HeLa cells via endocytosis. In addition, the empty vehicles have no toxicity in healthy cells and present antimicrobial activity.


Asunto(s)
Antineoplásicos/farmacología , Celulosa/análogos & derivados , Preparaciones de Acción Retardada , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Ácido Fólico/química , Microesferas , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Celulosa/química , Doxorrubicina/administración & dosificación , Femenino , Humanos , Ratones , Microscopía Confocal , Microscopía Electrónica de Rastreo , Estructura Molecular
13.
Mater Sci Eng C Mater Biol Appl ; 37: 271-7, 2014 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-24582249

RESUMEN

Polymeric pH- and thermo-sensitive microcontainers (MCs) were developed as a potential drug delivery system for cancer therapy. It is well known that cancer cells exhibit notable characteristics such as acidic pH due to glycolytic cycle and higher temperature due to their higher proliferation rate. Based on these characteristics, we constructed a dual pH- and thermo-sensitive material for specific drug release on the pathological tissue. The MC's fabrication is based on a two-step procedure, in which, the first step involves the core synthesis and the second one is related to the shell formation. The core consists of poly(methyl methacrylate (PMMA), while the shell consists of PMMA, poly(isopropylacrylamide), poly(acrylic acid) and poly(divinylbenzene). Three different types of MCs were synthesized based on the seed polymerization method. The synthesized MCs were characterized structurally by Fourier transform infrared and morphologically by scanning electron microscopy. Dynamic light scattering was also used to study their behavior in aqueous solution under different pH and temperature conditions. For the loading and release study, the anthracycline drug daunorubicin (DNR) was used as a model drug, and its release properties were evaluated under different pH and thermo-conditions. Cytotoxicity studies were also carried out against MCF-7 breast cancer and 3T3 mouse embryonic fibroblast cells. According to our results, the synthesized microcontainers present desired pH and thermo behavior and can be applied in drug delivery systems. It is worth mentioning that the synthesized microcontainers which incorporated the drug DNR exhibit higher toxicity than the free drug.


Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Polímeros/química , Células 3T3 , Resinas Acrílicas/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Supervivencia Celular/efectos de los fármacos , Daunorrubicina/administración & dosificación , Daunorrubicina/química , Daunorrubicina/toxicidad , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Ratones , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Tamaño de la Partícula , Polimetil Metacrilato/química , Estirenos/química , Temperatura
14.
Int J Pharm ; 461(1-2): 54-63, 2014 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-24286923

RESUMEN

This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Acrilatos/química , Animales , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/toxicidad , Reactivos de Enlaces Cruzados/química , Preparaciones de Acción Retardada , Doxorrubicina/farmacocinética , Doxorrubicina/toxicidad , Composición de Medicamentos , Femenino , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Inyecciones Intravenosas , Campos Magnéticos , Magnetismo , Ratones , Microesferas , Nanopartículas , Polímeros/química , Polimetil Metacrilato/química , Distribución Tisular , Compuestos de Vinilo/química
15.
Int J Pharm ; 465(1-2): 333-46, 2014 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-24583207

RESUMEN

Liposomes radiolabelling with diagnostic radionuclides is an excellent tool for studying pharmacokinetics with the view of developing liposome-based drug delivery agents. The aim of the present study is to evaluate the in vitro and in vivo behavior of a (99m)Tc-labeled liposome by applying either a direct labeling strategy via a carboxyl group, LP-COOH, or a surface chelating method via pyridyl ethyl cysteine compound (with the intermediate [99mTc(I)(CO)3(H2O)(3)](+)), LP-PEC. 99mTc-LP-COOH was obtained in high radiolabelling yield and radiochemical purity, while 99mTc(I)(CO)3-LP-PEC was initially purified before being in vitro and in vivo evaluated. 99mTc-LP-COOH was less stable in the presence of competitive for 99mTc ligands than 99mTc(I)(CO)3-LP-PEC. According to DLS measurements, the presence of serum as well as the applied radiolabelling conditions did not affect the liposomes' size. The different radiolabelling methods seemed to exert an influence on the biodistribution pattern of the liposomes with the 99mTc(I)(CO)3-LP-PEC showing slow blood clearance, which was also confirmed by in vivo scintigraphic imaging. Nevertheless, passive tumor targeting was attained at a similar extent no matter which radiolabelling technique was followed.


Asunto(s)
Lípidos/química , Neoplasias/diagnóstico por imagen , Radiofármacos , Compuestos de Tecnecio , Animales , Línea Celular Tumoral , Femenino , Humanos , Inyecciones Intravenosas , Liposomas , Ratones , Neoplasias/metabolismo , Tamaño de la Partícula , Cintigrafía , Radiofármacos/administración & dosificación , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Compuestos de Tecnecio/administración & dosificación , Compuestos de Tecnecio/síntesis química , Compuestos de Tecnecio/farmacocinética , Distribución Tisular
16.
J Colloid Interface Sci ; 433: 163-175, 2014 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-25128864

RESUMEN

HYPOTHESIS: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe3O4 (10±2nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted (99m)Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. EXPERIMENTS: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and ανß3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. FINDINGS: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted (99m)Tc-NPs poorly internalized in the tumor, while the targeted (99m)Tc-NPs-RGD, present 9-fold higher tumor accumulation at 1h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.


Asunto(s)
Antineoplásicos , Materiales Biocompatibles Revestidos , Medios de Contraste , Compuestos Férricos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma , Hipertermia Inducida , Integrina alfaVbeta3/biosíntesis , Nanopartículas/química , Proteínas de Neoplasias/biosíntesis , Tecnecio , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Medios de Contraste/química , Medios de Contraste/farmacología , Compuestos Férricos/química , Compuestos Férricos/farmacología , Glioblastoma/metabolismo , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Marcaje Isotópico , Ratones , Ratones SCID , Trasplante de Neoplasias , Propilaminas , Silanos/química , Tecnecio/química , Tecnecio/farmacología
17.
J Colloid Interface Sci ; 384(1): 198-206, 2012 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-22795041

RESUMEN

Biocompatible hollow poly(methyl acrylic acid-co-N-isopropylacrylamide-co-ethyleneglycol dimethacrylate)@cellulose succinate (P(MAA-co-NIPAAM-co-EGDMA)@CS) microspheres have been synthesized by employing uniform silica-MPS microspheres as template. Silica spheres were synthesized via Stöber method involving tetraethyl orthosilicate. The surface of resulting silica Stöber microspheres was modified using 3-methacryloxypropyltrimethoxysilane (MPS), a polymerizable silane coupling agent. The above reagent introduces carbon-carbon double bonds on microspheres' surface. This strategy uses the copolymerization of the following monomers, methacrylic acid (MAA), N-isopropyl acrylamide (NIPAAM) and the ethyleneglycol dimethacrylate (EGDMA), which was used as cross-linker, aiming at fabricating the first shell. Distillation precipitation polymerization method was carried out with 2,2-azobis(2-methylpropionitrile) as initiator in acetonitrile aiming at coating the inorganic microspheres with organic shell of the above-mentioned copolymer. In continuation, cellulose succinate and cellulose powder was absorbed through electrostatic interactions onto microspheres' surface and the isolated product was cross-linked through esteric bonds formation. The cellulose succinate hollow microspheres were obtained after the silica core removal. The resulting spheres were characterized by Fourier transform infrared spectroscopy and observed by scanning and transmission electron microscopy. Dynamic light scattering was used to study the hydrodynamic diameter of the synthesized microspheres. The anticancer drug daunorubicin was loaded in the spheres, and its release behavior was evaluated at acidic and slightly basic pH conditions, aiming at evaluating its behavior at the healthy and pathogenic tissues.


Asunto(s)
Antineoplásicos/química , Materiales Biocompatibles/síntesis química , Daunorrubicina/química , Portadores de Fármacos/síntesis química , Ácidos Polimetacrílicos/síntesis química , Polisacáridos/síntesis química , Absorción , Resinas Acrílicas/química , Humanos , Concentración de Iones de Hidrógeno , Cinética , Metacrilatos/química , Microscopía Electrónica de Transmisión , Microesferas , Polimerizacion , Silanos/química , Dióxido de Silicio/química , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie
18.
Phys Chem Chem Phys ; 10(5): 743-8, 2008 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-19791458

RESUMEN

Electron spins of molecular magnets are promising candidates for large scale quantum information processing because they exhibit a large number of low-lying excited states. In this paper X-band pulse electron paramagnetic resonance spectroscopy is used to determine the intrinsic relaxation times T1 and T2 of a molecular magnet with an S = 1/2 ground state, namely the neutral trinuclear oxo-centered iron (III) complex, [Fe3(micro3-O)(O2CPh)5(salox)(EtOH)(EtOH)(H2O)]. The temperature dependence of the spin-lattice relaxation time T1 between 4.5 and 11 K shows that the Orbach relaxation process is dominant with the first excited state lying 57 cm(-1) above the ground state, whereas the phase memory time T(M) is of the order of 2.6 micros and exhibits a modest temperature dependence. These results together with previous magnetic measurements give further insight into the magnetic properties of the complex. The coherent manipulation of the electron spins is also examined by means of transient nutation experiments.

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