Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Rep ; 9(1): 15844, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676822

RESUMO

Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.

2.
Med Sci (Paris) ; 35(8-9): 682-688, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31532381

RESUMO

Multi-elemental imaging of soft tissues using Laser-induced breakdown spectroscopy, also known as LIBS, allows for the direct visualization of the distribution of endogenous or exogenous elements within tissues. LIBS was used to image the kinetics of metal nanoparticles in elimination organs, but also the physiological distribution of biological elements in situ and the topography of chemicals or metals in exposed human tissues. Based on our experience and recent literature in the field of imaging the elemental content of animal and human specimens, this review describes the principle and characteristics of the instrument, technical considerations for setting up experiments with LIBS, its advantages, limitations and possibilities for pre-clinical and medical applications.


Assuntos
Diagnóstico por Imagem/tendências , Lasers , Análise Espectral/métodos , Alumínio/efeitos adversos , Alumínio/química , Animais , Diagnóstico por Imagem/métodos , Hipersensibilidade a Drogas/etiologia , Estudos de Avaliação como Assunto , Humanos
3.
Nanoscale ; 10(39): 18657-18664, 2018 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-30264838

RESUMO

We report in this study the in vivo biodistribution of ultra-small luminescent gold (Au) particles (∼1.5 nm core size; 17 kDa), so-called nanoclusters (NCs), stabilized by bidentate zwitterionic molecules in subcutaneous (s.c.) and orthotopic glioblastoma mice models. Particular investigations on renal clearance and tumor uptake were performed using highly sensitive advanced imaging techniques such as multi-elemental Laser-Induced Breakdown Spectroscopy (LIBS) imaging and in-line X-ray Synchrotron Phase Contrast Tomography (XSPCT). Results show a blood circulation time of 6.5 ± 1.3 min accompanied by an efficient and fast renal clearance through the cortex of the kidney with a 66% drop between 1 h and 5 h. With a similar size range, these Au NCs are 5 times more fluorescent than the well-described Au25GSH18 NCs in the near-infrared (NIR) region and present significantly stronger tumor uptake and retention illustrated by an in vivo s.c. tumor-to-skin ratio of 1.8 measured by non-invasive optical imaging and an ex vivo tumor-to-muscle of 6.1. This work highlights the pivotal role of surface coating in designing optimum Au NC candidates for cancer treatment.


Assuntos
Meios de Contraste , Glioblastoma/diagnóstico por imagem , Ouro , Nanopartículas Metálicas , Neoplasias Experimentais/diagnóstico por imagem , Tomografia Óptica , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Nus , Tomografia por Raios X
4.
Mod Pathol ; 31(3): 378-384, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29148536

RESUMO

Pathologists typically encounter many disparate exogenous materials in clinical specimens during their routine histopathological examinations, especially within the skin, lymph nodes, and lungs. These foreign substances may be free extracellular deposits or induce several clinical abnormalities or histopathological patterns. However, pathologists almost never investigate or report the chemical nature of exogenous metals in clinical specimens due to a lack of convenient and available technologies. In this paper, a novel strategy based on laser-induced breakdown spectroscopy (LIBS) technology is evaluated for in situ multi-elemental tissue imaging. The improved procedures allow visualization of the presence of chemical elements contained within paraffin-embedded specimens of medical interest with elemental images that are stackable with conventional histology images. We selected relevant medical situations for which the associated pathology reports were limited to the presence of lymphohistiocytic and inflammatory cells containing granules (a granuloma and a pseudolymphoma) or to lymph nodes or skin tissues containing pigments or foreign substances. Exogenous elements such as aluminum, titanium, copper, and tungsten were identified and localized within the tissues. The all-optical LIBS elemental imaging instrument that we developed is fully compatible with conventional optical microscopy used for pathology analysis. When combined with routine histopathological analysis, LIBS is a versatile technology that might help pathologists establish or confirm diagnoses for a wide range of medical applications, particularly when the nature of external agents present in tissues needs to be investigated.


Assuntos
Reação a Corpo Estranho/patologia , Espectrofotometria Atômica/métodos , Humanos , Lasers , Linfonodos/química , Linfonodos/ultraestrutura , Metais/análise , Inclusão em Parafina , Estudos Retrospectivos , Pele/química , Pele/ultraestrutura
5.
Environ Sci Pollut Res Int ; 24(3): 2197-2204, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27543127

RESUMO

Cave walls are affected by different kinds of alterations involving preservative issues in the case of ornate caves, in particular regarding the rock art covering the walls. In this context, coralloids correspond to a facies with popcorn-like aspect belonging to the speleothem family, mostly composed of calcium carbonate. The elemental characterization indicates the presence of elements that might be linked to the diagenesis and the expansion of the alterations as demonstrated by prior analyses on stalagmites. In this study, we report the use of laser-induced breakdown spectroscopy (LIBS) to characterize the elemental composition of one coralloid sample with a portable instrument allowing punctual measurements and a laboratory mapping setup delivering elemental images with spatial resolution at the micrometric scale, being particularly attentive to Mg, Sr, and Si identified as elements of interest. The complementarity of both instruments allows the determination of the internal structure of the coralloid. Although a validation based on a reference technique is necessary, LIBS data reveal that the external layer of the coralloid is composed of laminations correlated to variations of the LIBS signal of Si. In addition, an interstitial layer showing high LIBS signals for Fe, Al, and Si is interpreted to be a detrital clay interface between the external and the internal part of the coralloid. These preliminary results sustain a possible formation scenario of the coralloid by migration of the elements from the bedrock.


Assuntos
Carbonato de Cálcio , Cavernas , Análise Espectral , Arqueologia , Arte , Lasers
6.
Anal Chem ; 88(22): 10971-10978, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27750431

RESUMO

Chemical analysis of Chinese black ink on xuan paper is useful for the authentication of Asian artwork. The analysis has to be nondestructive and has to accommodate artworks of all sizes. We apply three analytical techniques, ArF laser-induced plume fluorescence, Fourier transform infrared (FTIR) spectroscopy, and portable X-ray fluorescence (pXRF) to analyze five commercial Chinese black inks on two kinds of xuan paper. The FTIR signal is found to be interfered by the substrate which is inevitable because the pigments diffuse extensively into the xuan fiber network. The XRF signal is shown to be feeble and no signal can be registered until the samples are stacked and when the analytes are present at tens of percent. In contrast, the plume fluorescence technique can detect the minor and trace signature elements. The method is based on a two-laser-pulse scheme performed on a high precision optical setup: the first 355 nm laser pulse ablates a thin layer of the ink to create a plume; the second 193 nm laser pulse induces multi analytes in the plume to fluoresce. Partial-least-squares discriminant analysis of the fluorescence spectra unambiguously sorts the ink-xuan combinations while the sampled area is not visibly damaged even under the microscope. The laser probe can handle samples of arbitrary size and shape, is air compatible, and no sample pretreatment is necessary.

7.
J Control Release ; 238: 103-113, 2016 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-27423325

RESUMO

Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment.


Assuntos
Gadolínio/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Radiossensibilizantes/uso terapêutico , Radioterapia Guiada por Imagem/métodos , Dióxido de Silício/uso terapêutico , Animais , Dano ao DNA/efeitos da radiação , Feminino , Gadolínio/química , Gadolínio/farmacocinética , Lasers , Macaca fascicularis , Imagem por Ressonância Magnética/métodos , Masculino , Camundongos , Nanopartículas/análise , Nanopartículas/química , Neoplasias/genética , Neoplasias/patologia , Radiossensibilizantes/química , Radiossensibilizantes/farmacocinética , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Nanomedicina Teranóstica/métodos
8.
Nano Lett ; 15(11): 7488-96, 2015 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-26418302

RESUMO

More than 50% of all cancer patients receive radiation therapy. The clinical delivery of curative radiation dose is strictly restricted by the proximal healthy tissues. We propose a dual-targeting strategy using vessel-targeted-radiosensitizing gold nanoparticles and conformal-image guided radiation therapy to specifically amplify damage in the tumor neoendothelium. The resulting tumor vascular disruption substantially improved the therapeutic outcome and subsidized the radiation/nanoparticle toxicity, extending its utility to intransigent or nonresectable tumors that barely respond to standard therapies.


Assuntos
Ouro/efeitos adversos , Nanopartículas Metálicas/efeitos adversos , Neoplasias/radioterapia , Neovascularização Patológica/tratamento farmacológico , Linhagem Celular Tumoral , Endotélio/efeitos dos fármacos , Endotélio/patologia , Endotélio/efeitos da radiação , Ouro/química , Humanos , Nanopartículas Metálicas/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neovascularização Patológica/patologia , Neovascularização Patológica/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Radioterapia Guiada por Imagem
9.
Small ; 11(37): 4900-9, 2015 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-26179212

RESUMO

The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle-based, calcium-responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA-USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA-USRPs on a multigram scale. The resulting platforms display the desired MRI activity­i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca(2+). Cell viability is probed with the MTT assay using HEK-293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA-USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser-induced breakdown spectroscopy experiments confirm accumulation of SCA-USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium-sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium-dependent physiological and pathological processes in a dynamic manner.


Assuntos
Cálcio , Meios de Contraste/química , Imagem por Ressonância Magnética/métodos , Nanopartículas/química , Tamanho da Partícula , Animais , Sobrevivência Celular/efeitos dos fármacos , Difusão Dinâmica da Luz , Feminino , Células HEK293 , Humanos , Injeções Intravenosas , Lasers , Ligantes , Camundongos Endogâmicos BALB C , Nanopartículas/toxicidade , Razão Sinal-Ruído , Análise Espectral , Titulometria , Testes de Toxicidade
10.
ACS Nano ; 9(3): 2477-88, 2015 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-25703068

RESUMO

We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.


Assuntos
Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacocinética , Meios de Contraste/química , Meios de Contraste/farmacocinética , Gadolínio/química , Gadolínio/farmacocinética , Nanopartículas Metálicas , Animais , Materiais Biocompatíveis/metabolismo , Materiais Biocompatíveis/toxicidade , Transporte Biológico , Meios de Contraste/metabolismo , Meios de Contraste/toxicidade , Gadolínio/metabolismo , Gadolínio/toxicidade , Humanos , Injeções , Córtex Renal/efeitos dos fármacos , Córtex Renal/metabolismo , Cinética , Camundongos , Modelos Moleculares , Conformação Molecular , Segurança , Raios X
11.
J Vis Exp ; (88)2014 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-24962015

RESUMO

Emission spectroscopy of laser-induced plasma was applied to elemental analysis of biological samples. Laser-induced breakdown spectroscopy (LIBS) performed on thin sections of rodent tissues: kidneys and tumor, allows the detection of inorganic elements such as (i) Na, Ca, Cu, Mg, P, and Fe, naturally present in the body and (ii) Si and Gd, detected after the injection of gadolinium-based nanoparticles. The animals were euthanized 1 to 24 hr after intravenous injection of particles. A two-dimensional scan of the sample, performed using a motorized micrometric 3D-stage, allowed the infrared laser beam exploring the surface with a lateral resolution less than 100 µm. Quantitative chemical images of Gd element inside the organ were obtained with sub-mM sensitivity. LIBS offers a simple and robust method to study the distribution of inorganic materials without any specific labeling. Moreover, the compatibility of the setup with standard optical microscopy emphasizes its potential to provide multiple images of the same biological tissue with different types of response: elemental, molecular, or cellular.


Assuntos
Gadolínio/química , Lasers , Nanopartículas Metálicas/química , Neoplasias Experimentais/química , Análise Espectral/métodos , Animais , Gadolínio/análise , Rim/química , Nanopartículas Metálicas/análise , Camundongos
12.
Phys Chem Chem Phys ; 16(3): 963-73, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24281437

RESUMO

Pulsed laser ablation has proved its reliability for the synthesis of nano-particles and nano-structured materials, including metastable phases and complex stoichiometries. The possible nucleation of the nanoparticles in the gas phase and their growth has been little investigated, due to the difficulty of following the gas composition as well as the thermodynamic parameters. We show that such information can be obtained from the optically active plasma during its short lifetime, only a few microseconds for each laser pulse, as a result of a quick quenching due to the liquid environment. For this purpose, we follow the laser ablation of an α-Al2O3 target (corindon) in water, which leads to the synthesis of nanoparticles of γ-Al2O3. The AlO blue-green emission and the Al(I) (2)P(0)-(2)S doublet emission provide the electron density, the density ratio between the Al atoms and AlO molecules, and the rotational and vibrational temperatures of the AlO molecules. These diagnostic considerations are discussed in the framework of theoretical studies from the literature (density functional theory). We have found that starting from a hot atomized gas, the nucleation cannot occur in the first microseconds. We also raise the question of the influence of water on the control of the stoichiometry.

13.
Appl Spectrosc ; 65(3): 307-14, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21352651

RESUMO

A combination of laser-induced breakdown spectroscopy (LIBS) and artificial neural networks (ANNs) has been used for the identification of polymer materials, including polypropylene (PP), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyoxymethylene (POM), polyethylene (PE), polyamide or nylon (PA), polycarbonate (PC) and poly(methyl methacrylate) (PMMA). After optimization of the experimental setup and the spectrum acquisition protocol, successful identification rates between 81 and 100% were achieved using spectral features gathered from single spectra without averaging (1 second acquisition time) over a wide spectral range (240-820 nm). Furthermore, ten different materials based on PVC were tested using the identification procedure. Correct identifications were obtained as well. Sorting of the materials into sub-categories of PVC materials according to their charges (concentration in trace elements such as Ca) was performed. The demonstrated capacities fit, in practice, the needs of plastic-waste sorting and of producing high-grade recycled plastic materials.

14.
J Phys Chem B ; 114(8): 2988-96, 2010 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-20143802

RESUMO

Determining the number of fluorescent entities that are coupled to a given molecule (DNA, protein, etc.) is a key point of numerous biological studies, especially those based on a single molecule approach. Reliable methods are important, in this context, not only to characterize the labeling process but also to quantify interactions, for instance within molecular complexes. We combined fluorescence correlation spectroscopy (FCS) and photobleaching experiments to measure the effective number of molecules and the molecular brightness as a function of the total fluorescence count rate on solutions of cDNA (containing a few percent of C bases labeled with Alexa Fluor 647). Here, photobleaching is used as a control parameter to vary the experimental outputs (brightness and number of molecules). Assuming a Poissonian distribution of the number of fluorescent labels per cDNA, the FCS-photobleaching data could be easily fit to yield the mean number of fluorescent labels per cDNA strand (approximately = 2). This number could not be determined solely on the basis of the cDNA brightness, because of both the statistical distribution of the number of fluorescent labels and their unknown brightness when incorporated in cDNA. The statistical distribution of the number of fluorophores labeling cDNA was confirmed by analyzing the photon count distribution (with the cumulant method), which showed clearly that the brightness of cDNA strands varies from one molecule to the other. We also performed complementary continuous photobleaching experiments and found that the photobleaching decay rate of Alexa Fluor 647 in the excited state decreases by about 30% when incorporated into cDNA, while its nonradiative decay rate is increased such that the brightness of individual Alexa labels is decreased by 25% compared to free Alexa dyes.


Assuntos
DNA Complementar/química , Corantes Fluorescentes/química , Fotodegradação , Soluções , Espectrometria de Fluorescência , Coloração e Rotulagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA