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1.
Int J Nanomedicine ; 16: 2219-2236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33762822

RESUMO

Introduction: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. Material and Method: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. Results: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. Conclusion: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.


Assuntos
Doxorrubicina/uso terapêutico , Gadolínio/química , Ouro/química , Nanotubos/química , Nanomedicina Teranóstica , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Endocitose , Humanos , Concentração Inibidora 50 , Imagem por Ressonância Magnética , Camundongos , Nanotubos/ultraestrutura , Neoplasias/tratamento farmacológico , Espectrofotometria Ultravioleta
2.
Nat Biomed Eng ; 5(3): 252-263, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33686281

RESUMO

Contrast agents for magnetic resonance imaging (MRI) improve anatomical visualizations. However, owing to poor image resolution in whole-body MRI, resolving fine structures is challenging. Here, we report that a nanoparticle with a polysaccharide supramolecular core and a shell of amorphous-like hydrous ferric oxide generating strong T1 MRI contrast (with a relaxivity coefficient ratio of ~1.2) facilitates the imaging, at resolutions of the order of a few hundred micrometres, of cerebral, coronary and peripheral microvessels in rodents and of lower-extremity vessels in rabbits. The nanoparticle can be synthesized at room temperature in aqueous solution and in the absence of surfactants, has blood circulation and renal clearance profiles that prevent opsonization, and leads to better imaging performance than Dotarem (gadoterate meglumine), a clinically approved gadolinium-based MRI contrast agent. The nanoparticle's biocompatibility and imaging performance may prove advantageous in a broad range of preclinical and clinical applications of MRI.


Assuntos
Dextranos/química , Compostos Férricos/química , Imagem por Ressonância Magnética/métodos , Nanopartículas/química , Animais , Materiais Biocompatíveis/química , Meios de Contraste/química , Gadolínio/química , Meglumina/química , Camundongos , Camundongos Endogâmicos BALB C , Microvasos/patologia , Compostos Organometálicos/química , Tamanho da Partícula , Polissacarídeos/química , Coelhos , Ratos , Ratos Sprague-Dawley
3.
Molecules ; 26(4)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671351

RESUMO

The strong demand for rare-earth elements (REEs) is driven by their wide use in high-tech devices. New processes have to be developed for valorizing low-grade ores or alternative metal sources (such as wastes and spent materials). The present work contributed to the development of new sorbents for the recovery of rare earth ions from aqueous solutions. Functionalized mesoporous silica composite was synthesized by grafting diethylenetriamine onto composite support. The physical and chemical properties of the new sorbent are characterized using BET, TGA, elemental analysis, titration, FTIR, and XPS spectroscopies to identify the reactive groups (amine groups: 3.25 mmol N g-1 and 3.41 by EA and titration, respectively) and their mode of interaction with Nd(III) and Gd(III). The sorption capacity at the optimum pH (i.e., 4) reaches 0.9 mmol Nd g-1 and 1 mmol Gd g-1. Uptake kinetics are modeled by the pseudo-first-order rate equation (equilibrium time: 30-40 min). At pH close to 4-5, the sorbent shows high selectivity for rare-earth elements against alkali-earth elements. This selectivity is confirmed by the efficient recovery of REEs from acidic leachates of gibbsite ore. After elution (using 0.5 M HCl solutions), selective precipitation (using oxalate solutions), and calcination, pure rare earth oxides were obtained. The sorbent shows promising perspective due to its high and fast sorption properties for REEs, good recycling, and high selectivity.


Assuntos
Aminas/química , Gadolínio/química , Neodímio/química , Polímeros/química , Dióxido de Silício/química , Adsorção , Concentração de Íons de Hidrogênio , Resíduos Industriais/análise , Cinética , Espectroscopia Fotoeletrônica , Porosidade , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier
4.
Nat Commun ; 12(1): 145, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420008

RESUMO

Radiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.


Assuntos
Complexos de Coordenação/administração & dosagem , Morte Celular Imunogênica/efeitos dos fármacos , Nanopartículas/administração & dosagem , Neoplasias/radioterapia , Radioimunoterapia/métodos , Animais , Linhagem Celular Tumoral/transplante , Terapia Combinada/métodos , Complexos de Coordenação/química , Modelos Animais de Doenças , Feminino , Gadolínio/administração & dosagem , Gadolínio/química , Hemina/administração & dosagem , Hemina/química , Humanos , Morte Celular Imunogênica/efeitos da radiação , Camundongos , Nanopartículas/química , Neoplasias/imunologia , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Estresse Oxidativo/efeitos da radiação , Polímeros/química
5.
Molecules ; 26(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467192

RESUMO

The aim of this work is to study the effect of the phase composition of the synthesized Fe2O3-Gd2O3 nanoparticles on the efficiency of using magnetic hyperthermia as a basis for experiments. This class of structures is one of the most promising materials for biomedical applications and magnetic resonance imaging. In the course of the study, the dynamics of phase transformations of nanoparticles Fe2O3 → Fe2O3/GdFeO3 → GdFeO3 were established depending on the annealing temperature. It has been determined that the predominance of the GdFeO3 phase in the structure of nanoparticles leads to an increase in their size from 15 to 40 nm. However, during experiments to determine the resistance to degradation and corrosion, it was found that GdFeO3 nanoparticles have the highest corrosion resistance. During the hyperthermal tests, it was found that a change in the phase composition of nanoparticles, as well as their size, leads to an increase in the heating rate of nanoparticles, which can be further used for practical purposes.


Assuntos
Compostos Férricos/química , Gadolínio/química , Temperatura Alta , /química , Corrosão
6.
J Mater Chem B ; 9(4): 1138-1150, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33432964

RESUMO

Gold nanomaterials are widely used in biomedical research as drug delivery systems, imaging agents and therapeutic materials owing to their unique physicochemical properties and high biocompatibility. In this study, we prepared ultra-small gold nanoparticles (AuNPs) and induced them with gadolinium ions to form a spherical self-assembly. The nanoparticles were coupled with matrix metalloproteinase-2 (MMP-2) and loaded with the photosensitive drug IR820 for photothermal/photodynamic combination therapy of liver cancer. The formed nanoprobes were metabolised in vivo via degradation under dual-mode real-time imaging because of their acid response degradation characteristics. In addition, the nanoprobe showed excellent tumour-targeting ability due to the presence of surface-modified MMP-2. In vivo treatment experiments revealed that the nanoprobes achieved enhanced photodynamic/photothermal combination therapy under laser irradiation and significantly inhibited tumour growth. Therefore, the nanoprobes have great potential for anti-tumour therapy guided by dual-mode real-time imaging of liver cancer.


Assuntos
Antineoplásicos/farmacologia , Gadolínio/farmacologia , Ouro/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas Metálicas/química , Fotoquimioterapia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Gadolínio/química , Ouro/química , Humanos , Íons/química , Íons/farmacologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Propriedades de Superfície , Células Tumorais Cultivadas
7.
Anal Chem ; 93(3): 1237-1241, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33378151

RESUMO

The development of three-dimensional (3D) single-cell imaging and protein quantitative methods can provide more comprehensive information for diagnoses. We report the design and synthesis of a multisignal nanoprobe (AuGdNC@BSA-CV) for single-cell 3D imaging and quantifying the integrin αIIbß3 using correlated synchrotron radiation soft X-ray tomography microscopy and an iterative tomographic algorithm termed equally sloped tomography for the first time. Moreover, on the basis of the Au or Gd content of our nanoprobe, the number of integrin αIIbß3 on a single cell also can be accurately quantified (1.5 × 107 per cell) via inductively coupled plasma mass spectrometry.


Assuntos
Imageamento Tridimensional , Integrinas/análise , Nanopartículas/química , Análise de Célula Única , Tomografia Computadorizada por Raios X , Linhagem Celular Tumoral , Gadolínio/química , Ouro/química , Humanos , Soroalbumina Bovina/química , Síncrotrons
8.
ACS Appl Mater Interfaces ; 12(51): 56874-56885, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33326207

RESUMO

Radiotherapy is the main treatment for cancer patients. A major concern in radiotherapy is the radiation resistance of some tumors, such as human nonsmall cell lung cancer. However, the radiation dose delivered to the tumors is often limited by the possibility of collateral damage to surrounding healthy tissues. A new and efficient gadolinium-based nanoparticle, AGuIX, has recently been developed for magnetic resonance imaging-guided radiotherapy and has been proven to act as an efficient radiosensitizer. The amplified radiation effects of AGuIX nanoparticles appear to be due to the emission of low-energy photoelectrons and Auger electron interactions. We demonstrated that AGuIX nanoparticles exacerbated radiation-induced DNA double-strand break damage and reduced DNA repair in the H1299 nonsmall cell lung cancer cell line. Furthermore, we observed a significant improvement in tumor cell damage and growth suppression, under radiation therapy, with the AGuIX nanoparticles in a H1299 mouse xenograft model. This study paves the way for research into the radiosensitization mechanism of AGuIX nanoparticles and provides a scientific basis for the use of AGuIX nanoparticles as radiosensitizing drugs.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Gadolínio/química , Gadolínio/efeitos da radiação , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos Nus , Radiação Ionizante , Radiossensibilizantes/química , Radiossensibilizantes/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
9.
PLoS One ; 15(12): e0243839, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315914

RESUMO

The preoperative imaging-based differentiation of primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBs) is of high importance since the therapeutic strategies differ substantially between these tumors. In this study, we investigate whether the gamma distribution (GD) model is useful in this differentiation of PNCSLs and GBs. Twenty-seven patients with PCNSLs and 57 patients with GBs were imaged with diffusion-weighted imaging using 13 b-values ranging from 0 to 1000 sec/mm2. The shape parameter (κ) and scale parameter (θ) were obtained with the GD model. Fractions of three different areas under the probability density function curve (f1, f2, f3) were defined as follows: f1, diffusion coefficient (D) <1.0×10-3 mm2/sec; f2, D >1.0×10-3 and <3.0×10-3 mm2/sec; f3, D >3.0 × 10-3 mm2/sec. The GD model-derived parameters were compared between PCNSLs and GBs. Receiver operating characteristic (ROC) curve analyses were performed to assess diagnostic performance. The correlations with intravoxel incoherent motion (IVIM)-derived parameters were evaluated. The PCNSL group's κ (2.26 ± 1.00) was significantly smaller than the GB group's (3.62 ± 2.01, p = 0.0004). The PCNSL group's f1 (0.542 ± 0.107) was significantly larger than the GB group's (0.348 ± 0.132, p<0.0001). The PCNSL group's f2 (0.372 ± 0.098) was significantly smaller than the GB group's (0.508 ± 0.127, p<0.0001). The PCNSL group's f3 (0.086 ± 0.043) was significantly smaller than the GB group's (0.144 ± 0.062, p<0.0001). The combination of κ, f1, and f3 showed excellent diagnostic performance (area under the curve, 0.909). The f1 had an almost perfect inverse correlation with D. The f2 and f3 had very strong positive correlations with D and f, respectively. The GD model is useful for the differentiation of GBs and PCNSLs.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/diagnóstico , Glioblastoma/diagnóstico por imagem , Glioblastoma/diagnóstico , Linfoma/diagnóstico por imagem , Linfoma/diagnóstico , Imagem por Ressonância Magnética , Modelos Biológicos , Idoso , Diagnóstico Diferencial , Feminino , Gadolínio/química , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Curva ROC
10.
Int J Nanomedicine ; 15: 4691-4703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636625

RESUMO

Purpose: Gd-encapsulated carbonaceous dots (Gd@C-dots) have excellent stability and magnetic properties without free Gd leakage, therefore they can be considered as a safe alternative T1 contrast agent to commonly used Gd complexes. To improve their potential for cancer diagnosis and treatment, affibody-modified Gd@C-dots targeting non-small-cell lung cancer (NSCLC) EGFR-positive tumors with enhanced renal clearance were developed and synthesized. Materials and Methods: Gd@C-dots were developed and modified with Ac-Cys-ZEGFR:1907 through EDC/NHS. The size, morphology, and optical properties of the Gd@C-dots and Gd@C-dots-Cys-ZEGFR:1907 were characterized. Targeting ability was evaluated by in vitro and in vivo experiments, respectively. Residual gadolinium concentration in major organs was detected with confocal imaging and inductively coupled plasma mass spectrometry (ICP-MS) ex vivo. H&E staining was used to assess the morphology of these organs. Results: Gd@C-dots with nearly 20 nm in diameter were developed and modified with Ac-Cys-ZEGFR:1907. EGFR expression in HCC827 cells was higher than NCI-H520. In cell uptake assays, EGFR-expressing HCC827 cells exhibited significant MR T1WI signal enhancement when compared to NCI-H520 cells. Cellular uptake of Gd@C-dots-Cys-ZEGFR:1907 was reduced, when Ac-Cys-ZEGFR:1907 was added. In vivo targeting experiments showed that the probe signal was significantly higher in HCC827 than NCI-H520 xenografts at 1 h after injection. In contrast to Gd@C-dots, Gd@C-dots-Cys-ZEGFR:1907 nanoparticles can be efficiently excreted through renal clearance. No morphological changes were observed by H&E staining in the major organs after injection of Gd@C-dots-Cys-ZEGFR:1907. Conclusion: Gd@C-dots-Cys-ZEGFR:1907 is a high-affinity EGFR-targeting probe with efficient renal clearance and is therefore a promising contrast agent for clinical applications such as diagnosis and treatment of NSCLC EGFR-positive malignant tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Meios de Contraste/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Pontos Quânticos/química , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Meios de Contraste/química , Receptores ErbB/metabolismo , Feminino , Gadolínio/química , Gadolínio/farmacocinética , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Nus , Nanopartículas/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Phys Med Biol ; 65(19): 195005, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32575086

RESUMO

Gadolinium aluminum gallium garnet (GAGG) is a promising scintillator crystal for positron emission tomography (PET) detectors owing to its advantages of energy resolution, light yield, and absence of intrinsic radiation. However, a large portion of the incident photons undergoes Compton scattering within GAGG crystal because of its low stopping power compared to that of lutetium-based crystals such as Lu2SiO5 (LSO). Inter-detector scattering (IDS) and inter-crystal scattering (ICS) result in loss of sensitivity and image quality of PET, respectively. We performed a Monte Carlo simulation study to evaluate IDS recovery in our currently developing brain-dedicated PET, and extended the idea to ICS recovery. We also compared the impact of the recoveries on LSO- and GAGG-based PET scanners. We measured the sensitivity and spatial resolution of the brain PET, and analyzed the image quality using a lesion phantom, a hot-rod phantom, and a 2D Hoffman phantom with applying IDS or ICS recovery. IDS recovery increased the PET sensitivity and improved the noise level of the reconstructed images. ICS recovery enhanced the spatial resolution and the contrast of the images was improved. As the occurrence rates of IDS and ICS were higher in GAGG than in LSO, the overall impact of IDS or ICS recovery was significant in GAGG. In conclusion, we showed that the proportional method would be suitable for IDS and ICS recoveries of PET, and emphasized the importance of ICS and IDS recoveries for PET using crystals with low stopping power.


Assuntos
Encéfalo/diagnóstico por imagem , Gadolínio/química , Gálio/química , Lutécio/química , Imagens de Fantasmas , Tomografia por Emissão de Pósitrons/métodos , Compostos de Silício/química , Desenho de Equipamento , Humanos , Processamento de Imagem Assistida por Computador/métodos , Método de Monte Carlo , Fótons , Contagem de Cintilação/instrumentação
12.
J Med Chem ; 63(13): 6909-6923, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32545964

RESUMO

Advancements in recanalization therapies have rendered reperfusion injury an important challenge for stroke management. It is essential to work toward effective therapeutics that protect the ischemic brain from reperfusion injury. Here, we report a new concept of neuroprognostic agents, which combine molecular diagnostic imaging and targeted neuroprotection for treatment of reperfusion injury after stroke. These neuroprognostic agents are inflammation-targeted gadolinium compounds conjugated with nonsteroidal anti-inflammatory drugs (NSAIDs). Our results demonstrated that gadolinium-based MRI contrast agents conjugated with NSAIDs suppressed the increase in cyclooxygenase-2 (COX-2) levels, ameliorated glial activation, and neuron damage that are phenotypic for stroke by mitigating neuroinflammation, which prevented reperfusion injury. In addition, this study showed that the neuroprognostic agents are promising T1 molecular MRI contrast agents for detecting precise reperfusion injury locations at the molecular level. Our results build on this new concept of neuroprognostics as a novel management strategy for ischemia-reperfusion injury, combining neuroprotection and molecular diagnostics.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Gadolínio/química , Imagem por Ressonância Magnética , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/prevenção & controle , Acidente Vascular Cerebral/complicações , Animais , Anti-Inflamatórios não Esteroides/química , Meios de Contraste/química , Ciclo-Oxigenase 2/química , Masculino , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/química , Conformação Proteica , Ratos , Ratos Sprague-Dawley
13.
Phys Chem Chem Phys ; 22(24): 13358-13362, 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32478770

RESUMO

Label-based functional studies of biomolecules in their native environment require labeling reactions inside living cells. In cell spin labeling using alkyne-azide click chemistry with a Gd3+-DOTAM-azide complex is shown to provide high spin label stability and narrow EPR lines for EPR spectroscopic detection of a spin labeled protein in living cells at ambient temperatures.


Assuntos
Escherichia coli/química , Gadolínio/química , Proteínas de Fluorescência Verde/análise , Marcadores de Spin , Acetamidas/química , Alquinos/química , Azidas/química , Química Click , Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/citologia , Compostos Heterocíclicos com 1 Anel/química , Estrutura Molecular
14.
Anal Chim Acta ; 1113: 18-25, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32340665

RESUMO

Magnetic trapping has been employed in the development of analytical methods owing to its ease and simplicity in handling samples. Nevertheless, the generation of functional probes is usually time consuming. A new and simple affinity method that uses gadolinium ion (Gd3+), a magnetic ion, as affinity probe for magnetic tapping of pathogenic bacteria was demonstrated in the present study. Escherichia coli O157:H7, Staphylococcus aureus, and Acinetobacter baumannii were selected as model bacteria. The model bacteria were magnetically isolated after incubation in Tris buffer (pH 8) containing Gd3+ (0.1 M) under microwave heating (power: 180 W, 90 s × 3). The resultant Gd3+-bacterium conjugates possessed sufficient magnetism, resulting in magnetic aggregations by an external magnet (∼4,000 Gauss). For ease of magnetic isolation, the sample containing Gd3+-bacterium complexes was stirred by a small magnet. After 1 h, the magnet attached with precipitates, i.e., Gd3+-bacterium conjugates, was readily removed using a pair of tweezers. The bacteria in the resultant conjugates were characterized by matrix-assisted laser desorption/ionization mass spectrometry. The limits of detection of the current approach toward E. coli O157:H7, S. aureus, and A. baumannii in complex samples were ∼104-105 cells mL-1.


Assuntos
Acinetobacter baumannii/isolamento & purificação , Técnicas Bacteriológicas/métodos , Escherichia coli O157/isolamento & purificação , Gadolínio/química , Staphylococcus aureus/isolamento & purificação , Acinetobacter baumannii/química , Animais , Sangue/microbiologia , Bovinos , Complexos de Coordenação/química , Difosfatos/química , Escherichia coli O157/química , Limite de Detecção , Fenômenos Magnéticos , Microbiologia do Solo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Staphylococcus aureus/química
15.
Chem Commun (Camb) ; 56(26): 3729-3732, 2020 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129331

RESUMO

The metal hydration state within a designed coiled coil can be progressively tuned across the full integer range (3 → 0 aqua ligands), by careful choice of a second sphere terminal residue, including the lesser used Trp. Potential implications include a four-fold change in MRI relaxivity when applied to lanthanide coiled coils.


Assuntos
Complexos de Coordenação/química , Gadolínio/química , Peptídeos/química , Sequência de Aminoácidos , Sítios de Ligação , Ligação Proteica
16.
Sci Rep ; 10(1): 4909, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32184466

RESUMO

No imaging modality can be used to evaluate Fontan-associated liver disease (FALD). We retrospectively reviewed hepatic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) characteristics of patients within 1 year post-Fontan procedure, and we evaluated the association between hepatic imaging abnormalities and clinical parameters, including follow-up cardiac catheterization and laboratory test findings. The EOB-MR images were graded, based on the extent of the decreased enhancement, as "normal" (Grade 1), "segmental" (Grade 2), "regional" (Grade 3), and "diffuse" (Grade 4). We enrolled 37 patients (mean age, 3.5 ± 1.0 years): 9 patients had Grade 1 or 2; 14 patients, Grade 3; and 14 patients, Grade 4. EOB-MRI revealed characteristic reticular or mosaic patterns of diminished enhancement (i.e. "frog spawn" appearance). Ultrasonography did not detect diminished enhancement or "frog spawn" appearance. A trend existed toward increased grade severity in imaging with increased central venous pressure, pulmonary vascular resistance, and gamma-glutamyltransferase levels. Noninvasive EOB-MRI revealed the characteristic pattern of diminished enhancement, which was correlated with certain clinical parameters indicative of Fontan physiology and liver dysfunction. Early-stage FALD may occur soon after the Fontan procedure and is associated with increased pressure in the inferior vena cava and hepatic veins.


Assuntos
Gadolínio/química , Imagem por Ressonância Magnética/métodos , Ácido Pentético/análogos & derivados , Ácido Pentético/química , Criança , Pré-Escolar , Feminino , Humanos , Hepatopatias/diagnóstico por imagem , Masculino , Estudos Retrospectivos
17.
Nanotechnology ; 31(25): 255601, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32126545

RESUMO

To enhance the therapeutic efficiency and reduce side effects from drug delivery and chemotherapy, image-guided nanoscale systems have attracted tremendous attention in recent decades. In this study, we developed a novel method to fabricate a colchicine/gadolinium-loaded tubulin self-assembly nanocarrier (Col-Gd@Tub NC) for the image-guided chemotherapy of glioma. The Col-Gd@Tub NCs were spontaneously formed via tubulin self-assembly and were subsequently functionalized by colchicine and gadolinium elements. These resultant Col-Gd@Tub NCs with a diameter of 45 nm exhibited uniform particle size distribution and favorable stability without any leakage of gadolinium in water. Meanwhile, the introduction of gadolinium endowed Col-Gd@Tub NCs with high T 1-weighted MRI performance in vitro. After tail vein injection, Col-Gd@Tub NCs exhibited excellent MRI contrast capability and relatively long circulation time (∼12 h) and were finally cleared out from the bladder. More significantly, the binding colchicine still exerted an anti-tumor effect after the Col-Gd@Tub NCs were taken up by the tumor cells. These results show that the Col-Gd@Tub NCs may be served as a versatile nanoscale platform for the integration of biomedical imaging probes and therapeutic molecules for tumor therapy.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Colchicina/administração & dosagem , Gadolínio/química , Glioma/tratamento farmacológico , Tubulina (Proteína)/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Colchicina/química , Colchicina/farmacologia , Difusão Dinâmica da Luz , Feminino , Glioma/diagnóstico por imagem , Células HEK293 , Humanos , Imagem por Ressonância Magnética , Nanopartículas Metálicas , Camundongos , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Inorg Chem ; 59(7): 4909-4923, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32162905

RESUMO

Photodynamic therapy (PDT) is commonly employed in clinics to treat the cancer, but because of the hypoxic tumor microenvironment prevalent inside tumors, PDT therapeutic efficiency is not adequate hence limiting the effectiveness of PDT. Therefore, we designed a nanocomposite consisting of reduced nanographene oxide (rGO) modified with polyethylene glycol (PEG), manganese dioxide (MnO2), upconversion nanoparticles (UCNPs), and Chlorin e6 (Ce6) to spark oxygen production from H2O2 with the aim of relieving the tumor hypoxic microenvironments. For in vivo tumor PDT and photothermal therapy (PTT), UCNPs-Ce6-labeled rGO-MnO2-PEG nanocomposites were used as a therapeutic agent, augmenting the therapeutic efficiency of PDT via redox progression through the catalytic H2O2 decomposition pathway and further achieving excellent tumor inhibition. It is important to mention that degradation of MnO2 in an acidic cellular microenvironment leads to the creation of a massive volume of Mn2+ which was employed as a contrast mediator for magnetic resonance imaging (MRI). Our research postulates an approach to spark O2 formation through an internal stimulus to augment the efficiency of MRI- and computerized tomography (CT)-imaging-guided PDT and PTT.


Assuntos
Antineoplásicos/uso terapêutico , Nanocompostos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Feminino , Fluoretos/química , Fluoretos/efeitos da radiação , Fluoretos/uso terapêutico , Gadolínio/química , Gadolínio/efeitos da radiação , Gadolínio/uso terapêutico , Grafite/química , Grafite/uso terapêutico , Humanos , Raios Infravermelhos , Compostos de Manganês/química , Compostos de Manganês/uso terapêutico , Camundongos , Nanocompostos/química , Nanopartículas/química , Óxidos/química , Óxidos/uso terapêutico , Oxigênio/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Porfirinas/química , Porfirinas/efeitos da radiação , Microambiente Tumoral/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Biomater Sci ; 8(7): 1802-1814, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32163070

RESUMO

Upconversion nanoparticles (UCNPs) have been widely employed for tumor imaging using magnetic resonance imaging (MRI) and upconversion luminescence (UCL) imaging. The short blood clearance time and immunogenicity of UCNPs have limited their further application in vivo. We have designed UCNPs camouflaged with an exterior red blood cell (RBC) membrane coating (RBC-UCNPs) to solve these problems. Moreover, because of some intrinsic disadvantages of MRI and UCL imaging, we investigated the use of pretargeted RBC-UCNPs for positron-emission tomography (PET) imaging to obtain more comprehensive information. Our data showed that RBC-UCNPs retained the immunity feature from the source cells and the superior optical and chemical features from the pristine UCNP cores. The tumor-targeting ability of RBC-UCNPs was enhanced by binding 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)-2000] (DSPE-PEG-FA) molecules onto the cell membranes. PET imaging with short half-life radionuclides to visualize the RBC-UCNPs was successfully realized by a combination of pre-targeting and in vivo click chemistry. Blood chemistry, hematology, and histologic analysis suggested good in vivo biocompatibility of the RBC-UCNPs. Our method provides a new potential biomedical application of biomimetic nanoparticles.


Assuntos
Membrana Eritrocítica/química , Ácido Fólico/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Animais , Materiais Biomiméticos/química , Linhagem Celular Tumoral , Química Click , Feminino , Fluoretos/química , Gadolínio/química , Humanos , Imagem por Ressonância Magnética , Camundongos , Imagem Multimodal , Nanopartículas/química , Transplante de Neoplasias , Tomografia por Emissão de Pósitrons , Itérbio/química
20.
Chemistry ; 26(27): 6056-6063, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32133687

RESUMO

The properties of LnIII -HPDO3A complexes as relaxation enhancers and paraCEST agents are essentially related to the hydroxylpropyl moiety. A series of three HPDO3A derivatives, with small modifications to the hydroxyl arm, were herein investigated to understand how heightened control can be gained over the parameters involved in the design of these agents. A full 1 H and 17 O-NMR relaxometric analysis was conducted and demonstrated that increasing the length of the OH group from the lanthanide centre significantly enhanced the water exchange rate of the gadolinium complex, but with a subsequent reduction in kinetic stability. Alternatively, the introduction of an additional methyl group, which increased the steric bulk around the OH moiety, resulted in the formation of almost exclusively the TSAP isomer (95 %) as identified by 1 H-NMR of the europium complex. The gadolinium analogue of this complex also exhibited a very fast water exchange rate, but with no detectable loss of kinetic stability. This complex therefore demonstrates a notable improvement over Gd-HPDO3A.


Assuntos
Meios de Contraste/química , Gadolínio/química , Elementos da Série dos Lantanídeos/química , Imagem por Ressonância Magnética/métodos , Európio/química , Compostos Heterocíclicos/química , Cinética , Compostos Organometálicos/química , Água
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