Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.037
Filtrar
1.
ACS Appl Mater Interfaces ; 13(33): 39042-39054, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34375073

RESUMO

In developing a cluster-nanocarrier design, as a magnetic resonance imaging contrast agent, we have investigated the enhanced relaxivity of a manganese and iron-oxo cluster grafted within a porous polystyrene nanobead with increased relaxivity due to a higher surface area. The synthesis of the cluster-nanocarrier for the cluster Mn8Fe4O12(O2CC6H4CH═CH2)16(H2O)4, cross-linked with polystyrene (the nanocarrier), under miniemulsion conditions is described. By including a branched hydrophobe, iso-octane, the resulting nanobeads are porous and ∼70 nm in diameter. The increased surface area of the nanobeads compared to nonporous nanobeads leads to an enhancement in relaxivity; r1 increases from 3.8 to 5.2 ± 0.1 mM-1 s-1, and r2 increases from 11.9 to 50.1 ± 4.8 mM-1 s-1, at 9.4 teslas, strengthening the potential for T1 and T2 imaging. Several metrics were used to assess stability, and the porosity produced no reduction in metal stability. Synchrotron X-ray fluorescence microscopy was used to demonstrate that the nanobeads remain intact in vivo. In depth, physicochemical characteristics were determined, including extensive pharmacokinetics, in vivo imaging, and systemic biodistribution analysis.


Assuntos
Materiais Biocompatíveis/química , Meios de Contraste/química , Ferro/química , Manganês/química , Nanopartículas/química , Compostos Organometálicos/química , Poliestirenos/química , Animais , Materiais Biocompatíveis/farmacocinética , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/farmacocinética , Reagentes para Ligações Cruzadas/química , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Imagem Multimodal , Porosidade , Espectrometria por Raios X , Distribuição Tecidual
2.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207769

RESUMO

Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI.


Assuntos
Materiais Revestidos Biocompatíveis/química , Meios de Contraste/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Imageamento por Ressonância Magnética , Soroalbumina Bovina/química , Animais , Bovinos
3.
Chem Commun (Camb) ; 57(63): 7743-7757, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34286714

RESUMO

As a versatile quantification and tracking technology, 19F magnetic resonance imaging (19F MRI) provides quantitative "hot-spot" images without ionizing radiation, tissue depth limit, and background interference. However, the lack of suitable imaging agents severely hampers its clinical application. First, because the 19F signals are solely originated from imaging agents, the relatively low sensitivity of MRI technology requires high local 19F concentrations to generate images, which are often beyond the reach of many 19F MRI agents. Second, the peculiar physicochemical properties of many fluorinated compounds usually lead to low 19F signal intensity, tedious formulation, severe organ retention, etc. Therefore, the development of 19F MRI agents with high sensitivity and with suitable physicochemical and biological properties is of great importance. To this end, perfluoro-tert-butanol (PFTB), containing nine equivalent 19F and a modifiable hydroxyl group, has outperformed most perfluorocarbons as a valuable building block for high performance 19F MRI agents. Herein, we summarize the development and application of PFTB-based 19F MRI agents and analyze the strategies to improve their sensitivity and physicochemical and biological properties. In the context of PFC-based 19F MRI agents, we also discuss the challenges and prospects of PFTB-based 19F MRI agents.


Assuntos
Meios de Contraste/química , Imagem por Ressonância Magnética de Flúor-19 , Fluorcarbonetos/química , terc-Butil Álcool/química
4.
Int J Mol Sci ; 22(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34299271

RESUMO

Magnetic nanoparticles (MNPs) have a wide range of applications; an area of particular interest is magnetic particle imaging (MPI). MPI is an imaging modality that utilizes superparamagnetic iron oxide particles (SPIONs) as tracer particles to produce highly sensitive and specific images in a broad range of applications, including cardiovascular, neuroimaging, tumor imaging, magnetic hyperthermia and cellular tracking. While there are hurdles to overcome, including accessibility of products, and an understanding of safety and toxicity profiles, MPI has the potential to revolutionize research and clinical biomedical imaging. This review will explore a brief history of MPI, MNP synthesis methods, current and future applications, and safety concerns associated with this newly emerging imaging modality.


Assuntos
Meios de Contraste/química , Diagnóstico por Imagem/métodos , Nanopartículas Magnéticas de Óxido de Ferro/química , Animais , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/patologia , Diagnóstico por Imagem/tendências , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Doenças do Sistema Nervoso/diagnóstico por imagem , Doenças do Sistema Nervoso/patologia
5.
Cell Mol Life Sci ; 78(17-18): 6119-6141, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34297166

RESUMO

Ultrasonic technologies show great promise for diagnostic imaging and drug delivery in theranostic applications. The development of functional and molecular ultrasound imaging is based on the technical breakthrough of high frame-rate ultrasound. The evolution of shear wave elastography, high-frequency ultrasound imaging, ultrasound contrast imaging, and super-resolution blood flow imaging are described in this review. Recently, the therapeutic potential of the interaction of ultrasound with microbubble cavitation or droplet vaporization has become recognized. Microbubbles and phase-change droplets not only provide effective contrast media, but also show great therapeutic potential. Interaction with ultrasound induces unique and distinguishable biophysical features in microbubbles and droplets that promote drug loading and delivery. In particular, this approach demonstrates potential for central nervous system applications. Here, we systemically review the technological developments of theranostic ultrasound including novel ultrasound imaging techniques, the synergetic use of ultrasound with microbubbles and droplets, and microbubble/droplet drug-loading strategies for anticancer applications and disease modulation. These advancements have transformed ultrasound from a purely diagnostic utility into a promising theranostic tool.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Portadores de Fármacos/química , Microbolhas/uso terapêutico , Ultrassonografia , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/terapia , Meios de Contraste/química , Humanos , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/terapia
6.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34067989

RESUMO

Magnetic resonance imaging (MRI) is often used to diagnose diseases due to its high spatial, temporal and soft tissue resolution. Frequently, probes or contrast agents are used to enhance the contrast in MRI to improve diagnostic accuracy. With the development of molecular imaging techniques, molecular MRI can be used to obtain 3D anatomical structure, physiology, pathology, and other relevant information regarding the lesion, which can provide an important reference for the accurate diagnosis and treatment of the disease in the early stages. Among existing contrast agents, smart or activatable nanoprobes can respond to selective stimuli, such as proving the presence of acidic pH, active enzymes, or reducing environments. The recently developed environment-responsive or smart MRI nanoprobes can specifically target cells based on differences in the cellular environment and improve the contrast between diseased tissues and normal tissues. Here, we review the design and application of these environment-responsive MRI nanoprobes.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Nanopartículas de Magnetita/química , Sondas Moleculares/química , Humanos
7.
PLoS One ; 16(6): e0252478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34101734

RESUMO

BACKGROUND: Gas exchange in COVID-19 pneumonia is impaired and vessel obstruction has been suspected to cause ventilation-perfusion mismatch. Dual-energy CT (DECT) can depict pulmonary perfusion by regional assessment of iodine uptake. OBJECTIVE: The purpose of this study was the analysis of pulmonary perfusion using dual-energy CT in a cohort of 27 consecutive patients with severe COVID-19 pneumonia. METHOD: We retrospectively analyzed pulmonary perfusion with DECT in 27 consecutive patients (mean age 57 years, range 21-73; 19 men and 8 women) with severe COVID-19 pneumonia. Iodine uptake (IU) in regions-of-interest placed into normally aerated lung, ground-glass opacifications (GGO) and consolidations was measured using a dedicated postprocessing software. Vessel enlargement (VE) within opacifications and presence of pulmonary embolism (PE) was assessed by subjective analysis. Linear mixed models were used for statistical analyses. RESULTS: Compared to normally aerated lung 106/151 (70.2%) opacifications without upstream PE demonstrated an increased IU, 9/151 (6.0%) an equal IU and 36/151 (23.8%) a decreased IU. The estimated mean iodine uptake (EMIU) in opacifications without upstream PE (GGO 1.77 mg/mL; 95%-CI: 1.52-2.02; p = 0.011, consolidations 1.82 mg/mL; 95%-CI: 1.56-2.08, p = 0.006) was significantly higher compared to normal lung (1.22 mg/mL; 95%-CI: 0.95-1.49). In case of upstream PE, EMIU of opacifications (combined GGO and consolidations) was significantly decreased compared to normal lung (0.52 mg/mL; 95%-CI: -0.07-1.12; p = 0.043). The presence of VE in opacifications correlated significantly with iodine uptake (p<0.001). CONCLUSIONS: DECT revealed the opacifications in a subset of patients with severe COVID-19 pneumonia to be perfused non-uniformly with some being hypo- and others being hyperperfused. Mean iodine uptake in opacifications (both ground-glass and consolidation) was higher compared to normally aerated lung except for areas with upstream pulmonary embolism. Vessel enlargement correlated with iodine uptake: In summary, in a cohort of 27 consecutive patients with severe COVID-19 pneumonia, dual-energy CT demonstrated a wide range of iodine uptake in pulmonary ground-glass opacifications and consolidations as a surrogate marker for hypo- and hyperperfusion compared to normally aerated lung. Applying DECT to determine which pathophysiology is predominant might help to tailor therapy to the individual patient´s needs.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Meios de Contraste/química , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
ACS Appl Mater Interfaces ; 13(24): 27945-27954, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34110788

RESUMO

Magnetic resonance angiography (MRA) is an important imaging technique that can be used to identify and characterize various types of vascular diseases. However, currently used molecular contrast agents are unsuitable for MRA due to the short intravascular retention time, the whole-body distribution, and the relatively low contrast effect. In this study, we developed a vascular analysis contrast agent (i.e., VasCA) for MRA, which is a simple and biocompatible 1:1 host-guest assembly of PEGylated ß-cyclodextrin and gadolinium chelate with renal clearable size and high relaxivity (r1 = 9.27 mM-1 s-1). Its biocompatibility was confirmed by in vivo animal studies as well as in vitro 3D cell culture. In a tumor-bearing rat model, VasCA circulated in the blood vessels much longer (4.3-fold increase) than gadoterate meglumine (Dotarem) and was mainly excreted by the renal system after intravenous injection. This feature of VasCA allows characterization of tumor microvasculature (e.g., feeding and draining vessels) as well as visualization of small vessels in the brain and body organs. Furthermore, after treatment with an angiogenesis inhibitor (i.e., sorafenib), VasCA revealed the vessel normalization process and allowed the assessment of viable and necrotic tumor regions. Our study provides a useful tool for diverse MRA applications, including tumor characterization, early-stage evaluation of drug efficacy, and treatment planning, as well as diagnosis of cardiovascular diseases.


Assuntos
Meios de Contraste/química , Angiografia por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Animais , Quelantes/química , Gadolínio/química , Células HaCaT , Células Hep G2 , Humanos , Masculino , Polietilenoglicóis/química , Ratos Sprague-Dawley , beta-Ciclodextrinas/química
9.
J Mater Chem B ; 9(24): 4863-4872, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34095943

RESUMO

This study is focused on the development of innovative sensors to non-invasively monitor the tissue implant status by Fast-Field-Cycling Magnetic Resonance Imaging (FFC-MRI). These sensors are based on oligo-histidine moieties that are conjugated to PLGA polymers representing the structural matrix for cells hosting scaffolds. The presence of 14N atoms of histidine causes a quadrupolar relaxation enhancement (also called Quadrupolar Peak, QP) at 1.39 MHz. This QP falls at a frequency well distinct from the QPs generated by endogenous semisolid proteins. The relaxation enhancement is pH dependent in the range 6.5-7.5, thus it acts as a reporter of the scaffold integrity as it progressively degrades upon lowering the microenvironmental pH. The ability of this new sensors to generate contrast in an image obtained at 1.39 MHz on a FFC-MRI scanner is assessed. A good biocompatibility of the histidine-containing scaffolds is observed after its surgical implantation in healthy mice. Over time the scaffold is colonized by endogenous fibroblasts and this process is accompanied by a progressive decrease of the intensity of the relaxation peak. In respect to the clinically used contrast agents this material has the advantage of generating contrast without the use of potentially toxic paramagnetic metal ions.


Assuntos
Imidazóis/química , Imageamento por Ressonância Magnética/métodos , Próteses e Implantes , Materiais Inteligentes/química , Animais , Meios de Contraste/química , Camundongos
10.
Chem Commun (Camb) ; 57(51): 6288-6291, 2021 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-34075954

RESUMO

The dual-mode bio-imaging nanoprobe TP-CQDs@MnO2, based on two-photon carbon quantum dots and MnO2, has been developed for the two-photon fluorescence and MR imaging of endogenous H2O2 in the tumor microenvironment, and it achieved high selectivity, a great signal-to-noise ratio, a limit of detection (LOD) of 1.425 pM for H2O2, and a two-photon tissue penetration depth of 280 µm.


Assuntos
Peróxido de Hidrogênio/metabolismo , Imageamento por Ressonância Magnética , Microscopia Confocal , Nanoestruturas/química , Carbono/química , Linhagem Celular , Meios de Contraste/química , Humanos , Peróxido de Hidrogênio/análise , Limite de Detecção , Compostos de Manganês/química , Óxidos/química , Pontos Quânticos/química , Razão Sinal-Ruído , Espectrometria de Fluorescência , Microambiente Tumoral
11.
J Med Chem ; 64(13): 9182-9192, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34152137

RESUMO

Liver-specific contrast agents (CAs) can improve the Magnetic resonance imaging (MRI) detection of focal and diffuse liver lesions by increasing the lesion-to-liver contrast. A novel Mn(II) complex, Mn-BnO-TyrEDTA, with a lipophilic group-modified ethylenediaminetetraacetic acid (EDTA) structure as a ligand to regulate its behavior in vivo, is superior to Gd-EOB-DTPA in terms of a liver-specific MRI contrast agent. An MRI study on mice demonstrated that Mn-BnO-TyrEDTA can be rapidly taken up by hepatocytes with a combination of hepatobiliary and renal clearance pathways. Bromosulfophthalein (BSP) inhibition imaging, biodistribution, and cellular uptake studies confirmed that the mechanism of hepatic targeting of Mn-BnO-TyrEDTA is the hepatic uptake of the amphiphilic anion contrast agent mediated by organic anion transporting polypeptides (OATPs) expressed by functional hepatocytes.


Assuntos
Meios de Contraste/farmacocinética , Complexos de Coordenação/farmacocinética , Ácido Edético/farmacocinética , Hepatócitos/metabolismo , Imageamento por Ressonância Magnética , Manganês/farmacocinética , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/síntese química , Meios de Contraste/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ácido Edético/química , Hepatócitos/química , Hepatócitos/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Manganês/química , Camundongos , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
12.
Theranostics ; 11(14): 6966-6982, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093865

RESUMO

Rationale: Sensitive and accurate imaging of cancer is essential for early diagnosis and appropriate treatment. For generally employed magnetic resonance imaging (MRI) in clinic, comprehending how to enhance the contrast effect of T 1 imaging is crucial for improving the sensitivity of cancer diagnosis. However, there is no study ever to reveal the clear mechanism of how to enhance the effect of T 1 imaging and accurate relationships of influencing factors. Herein, this study aims to figure out key factors that affect the sensitivity of T 1 contrast-enhanced MRI (CE-MRI), thereby to realize sensitive detection of tumors with low dose of CAs. Methods: Manganese oxide (MnO) nanoparticles (NPs) with various sizes and shapes were prepared by thermal decomposition. Factors impacting T 1 CE-MRI were investigated from geometric volume, surface area, crystal face to r 2/r 1 ratio. T 1 CE-MR imaging of liver, hepatic and subcutaneous tumors were conducted with MnO NPs of different shapes. Results: The surface area and occupancy rate of manganese ions have positive impacts on the sensitivity of T 1 CE-MRI, while volume and r 2/r 1 ratio have negative effects. MnO octahedrons have a high r 1 value of 20.07 mM-1s-1 and exhibit an excellent enhanced effect in liver T 1 imaging. ZDS coating facilitates tumor accumulation and cellular uptake, hepatic and subcutaneous tumors could be detected with MnO octahedrons at an ultralow dose of 0.4 mg [Mn]/kg, about 1/10 of clinical dose. Conclusions: This work is the first quantitative study of key factors affecting the sensitivity of T 1 CE-MRI of MnO nanoparticles, which can serve as a guidance for rational design of high-performance positive MRI contrast agents. Moreover, these MnO octahedrons can detect hepatic and subcutaneous tumors with an ultralow dose, hold great potential for sensitive and accurate diagnosis of cancer with lower cost, less dosages and side effects in clinic.


Assuntos
Meios de Contraste/química , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Compostos de Manganês/química , Nanopartículas Metálicas/química , Óxidos/química , Animais , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Compostos de Manganês/síntese química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Óxidos/síntese química , Tamanho da Partícula
13.
Inorg Chem ; 60(12): 8651-8664, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34110140

RESUMO

Four high-spin Fe(III) macrocyclic complexes, including three dinuclear and one mononuclear complex, were prepared toward the development of more effective iron-based magnetic resonance imaging (MRI) contrast agents. All four complexes contain a 1,4,7-triazacyclononane macrocyclic backbone with two hydroxypropyl pendant groups, an ancillary aryl or biphenyl group, and a coordination site for a water ligand. The pH potentiometric titrations support one or two deprotonations of the complexes, most likely deprotonation of hydroxypropyl groups at near-neutral pH. Variable-temperature 17O NMR studies suggest that the inner-sphere water ligand is slow to exchange with bulk water on the NMR time scale. Water proton T1 relaxation times measured for solutions of the Fe(III) complexes at pH 7.2 showed that the dinuclear complexes have a 2- to 3-fold increase in r1 relaxivity in comparison to the mononuclear complex per molecule at field strengths ranging from 1.4 T to 9.4 T. The most effective agent, a dinuclear complex with macrocycles linked through para-substitution of an aryl group (Fe2(PARA)), has an r1 of 6.7 mM-1 s-1 at 37 °C and 4.7 T or 3.3 mM-1 s-1 per iron center in the presence of serum albumin and shows enhanced blood pool and kidney contrast in mice MRI studies.


Assuntos
Meios de Contraste/química , Complexos de Coordenação/química , Compostos Férricos/química , Compostos Macrocíclicos/química , Imageamento por Ressonância Magnética , Animais , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacocinética , Compostos Férricos/farmacocinética , Humanos , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/farmacocinética , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Albumina Sérica Humana/química
14.
Cancer Imaging ; 21(1): 44, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187570

RESUMO

BACKGROUND: The motif RXDLXXL-based nanoprobes allow specific imaging of integrin αvß6, a protein overexpressed during tumorigenesis and tumor progression of various tumors. We applied a novel RXDLXXL-coupled cyclic arginine-glycine-aspartate (RGD) nonapeptide conjugated with ultrasmall superparamagnetic iron oxide nanoparticles (referred to as cFK-9-USPIO) for the application of integrin αvß6-targeted magnetic resonance (MR) molecular imaging for breast cancer. METHODS: A novel MR-targeted nanoprobe, cFK-9-USPIO, was synthesized by conjugating integrin αvß6-targeted peptide cFK-9 to N-amino (-NH2)-modified USPIO nanoparticles via a dehydration esterification reaction. Integrin αvß6-positive mouse breast cancer (4 T1) and integrin αvß6 negative human embryonic kidney 293 (HEK293) cell lines were incubated with cFK-9-AbFlour 647 (blocking group) or cFK-9-USPIO (experimental group), and subsequently imaged using laser scanning confocal microscopy (LSCM) and 3.0 Tesla magnetic resonance imaging (MRI) system. The affinity of cFK-9 targeting αvß6 was analyzed by calculating the mean fluorescent intensity in cells, and the nanoparticle targeting effect was measured by the reduction of T2 values in an in vitro MRI. The in vivo MRI capability of cFK-9-USPIO was investigated in 4 T1 xenograft mouse models. Binding of the targeted nanoparticles to αvß6-positive 4 T1 tumors was determined by ex vivo histopathology. RESULTS: In vitro laser scanning confocal microscopy (LSCM) imaging showed that the difference in fluorescence intensity between the targeting and blocking groups of 4 T1 cells was significantly greater than that in HEK293 cells (P < 0.05). The in vitro MRI demonstrated a more remarkable T2 reduction in 4 T1 cells than in HEK293 cells (P < 0.001). The in vivo MRI of 4 T1 xenograft tumor-bearing nude mice showed significant T2 reduction in tumors compared to controls. Prussian blue staining further confirmed that αvß6 integrin-targeted nanoparticles were specifically accumulated in 4 T1 tumors and notably fewer nanoparticles were detected in 4 T1 tumors of mice injected with control USPIO and HEK293 tumors of mice administered cFK-9-USPIO. CONCLUSIONS: Integrin αvß6-targeted nanoparticles have great potential for use in the detection of αvß6-overexpressed breast cancer with MR molecular imaging.


Assuntos
Antígenos de Neoplasias/metabolismo , Integrinas/metabolismo , Imageamento por Ressonância Magnética/métodos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Animais , Meios de Contraste/química , Dextranos/farmacologia , Feminino , Células HEK293 , Humanos , Nanopartículas de Magnetita , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Nat Commun ; 12(1): 3840, 2021 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158498

RESUMO

Histopathological level imaging in a non-invasive manner is important for clinical diagnosis, which has been a tremendous challenge for current imaging modalities. Recent development of ultra-high-field (UHF) magnetic resonance imaging (MRI) represents a large step toward this goal. Nevertheless, there is a lack of proper contrast agents that can provide superior imaging sensitivity at UHF for disease detection, because conventional contrast agents generally induce T2 decaying effects that are too strong and thus limit the imaging performance. Herein, by rationally engineering the size, spin alignment, and magnetic moment of the nanoparticles, we develop an UHF MRI-tailored ultra-sensitive antiferromagnetic nanoparticle probe (AFNP), which possesses exceptionally small magnetisation to minimize T2 decaying effect. Under the applied magnetic field of 9 T with mice dedicated hardware, the nanoprobe exhibits the ultralow r2/r1 value (~1.93), enabling the sensitive detection of microscopic primary tumours (<0.60 mm) and micrometastases (down to 0.20 mm) in mice. The sensitivity and accuracy of AFNP-enhanced UHF MRI are comparable to those of the histopathological examination, enabling the development of non-invasive visualization of previously undetectable biological entities critical to medical diagnosis and therapy.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Magnetismo , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Neoplasias/patologia , Células RAW 264.7 , Ratos Wistar , Transplante Heterólogo
16.
J Med Chem ; 64(9): 5874-5885, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33945286

RESUMO

Myeloperoxidase (MPO) is a key component of innate immunity but can damage tissues when secreted abnormally. We developed a new generation of a highly efficient MPO-activatable MRI probe (heMAMP) to report MPO activity. heMAMP has improved Gd stability compared to bis-5-HT-Gd-DTPA (MPO-Gd) and demonstrates no significant cytotoxicity. Importantly, heMAMP is more efficiently activated by MPO compared to MPO-Gd, 5HT-DOTA(Gd), and 5HT-DOTAGA-Gd. Molecular docking simulations revealed that heMAMP has increased rigidity via hydrogen bonding intramolecularly and improved binding affinity to the active site of MPO. In animals with subcutaneous inflammation, activated heMAMP showed a 2-3-fold increased contrast-to-noise ratio (CNR) compared to activated MPO-Gd and 4-10 times higher CNR compared to conventional DOTA-Gd. This increased efficacy was further confirmed in a model of unstable atherosclerotic plaque where heMAMP demonstrated a comparable signal increase and responsiveness to MPO inhibition at a 3-fold lower dosage compared to MPO-Gd, further underscoring heMAMP as a potential translational candidate.


Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética , Peroxidase/metabolismo , Animais , Aterosclerose/diagnóstico por imagem , Sítios de Ligação , Cálcio/química , Cálcio/metabolismo , Domínio Catalítico , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/metabolismo , Meios de Contraste/farmacologia , Modelos Animais de Doenças , Desenho de Fármacos , Feminino , Gadolínio DTPA/química , Gadolínio DTPA/metabolismo , Meia-Vida , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/química , Células RAW 264.7 , Razão Sinal-Ruído , Distribuição Tecidual , Zinco/química , Zinco/metabolismo
17.
Int J Nanomedicine ; 16: 3105-3119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33967577

RESUMO

Background: Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an "all-in-one" form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation. Materials and Methods: Herein, a high efficient "one-for-all" nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo. Results: The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo. Conclusion: The PFP@PPy nanodroplet as a "one-for-all" theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.


Assuntos
Meios de Contraste/química , Nanoestruturas/química , Neoplasias Experimentais/diagnóstico por imagem , Terapia Fototérmica/métodos , Ultrassonografia/métodos , Animais , Meios de Contraste/farmacologia , Feminino , Fluorcarbonetos/química , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Microbolhas , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Neoplasias Experimentais/terapia , Transição de Fase , Técnicas Fotoacústicas/métodos , Polímeros/química , Pirróis/química , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Mater Chem B ; 9(18): 3925-3934, 2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-33942817

RESUMO

Nanozymes, as a kind of artificial mimic enzymes, have superior catalytic capacity and stability. As lack of O2 in tumor cells can cause resistance to drugs, we designed drug delivery liposomes (MnO2-PTX/Ce6@lips) loaded with catalase-like nanozymes of manganese dioxide nanoparticles (MnO2 NPs), paclitaxel (PTX) and chlorin e6 (Ce6) to consume tumor's native H2O2 and produce O2. Based on the catalysis of MnO2 NPs, a large amount of oxygen was produced by MnO2-PTX/Ce6@lips to burst the liposomes and achieve a responsive release of the loaded drug (paclitaxel), and the released O2 relieved the chemoresistance of tumor cells and provided raw materials for photodynamic therapy. Subsequently, MnO2 NPs were decomposed into Mn2+ in an acidic tumor environment to be used as contrast agents for magnetic resonance imaging. The MnO2-PTX/Ce6@lips enhanced the efficacy of chemotherapy and photodynamic therapy (PDT) in bearing-tumor mice, even achieving complete cure. These results indicated the great potential of MnO2-PTX/Ce6@lips for the modulation of the TME and the enhancement of chemotherapy and PDT along with MRI tracing in the treatment of tumors.


Assuntos
Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/química , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Luz , Lipossomos/química , Imageamento por Ressonância Magnética , Compostos de Manganês/química , Camundongos , Nanopartículas/química , Nanoestruturas/química , Nanoestruturas/toxicidade , Neoplasias/diagnóstico por imagem , Óxidos/química , Oxigênio/química , Oxigênio/metabolismo , Paclitaxel/química , Paclitaxel/metabolismo , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química
19.
J Med Chem ; 64(11): 7565-7574, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33961422

RESUMO

The relevance of MRI as a diagnostic methodology has been expanding significantly with the development of molecular imaging. Partially, the credit for this advancement is due to the increasing potential and performance of targeted MRI contrast agents, which are able to specifically bind distinct receptors or biomarkers. Consequently, these allow for the identification of tissues undergoing a disease, resulting in the over- or underexpression of the particular molecular targets. Here we report a multimeric molecular probe, which combines the established targeting properties of the Arg-Gly-Asp (RGD) peptide sequence toward the integrins with three calcium-responsive, Gd-based paramagnetic moieties. The bifunctional probe showed excellent 1H MRI contrast enhancement upon Ca2+ coordination and demonstrated a longer retention time in the tissue due to the presence of the RGD moiety. The obtained results testify to the potential of combining bioresponsive contrast agents with targeting vectors to develop novel functional molecular imaging methods.


Assuntos
Meios de Contraste/química , Integrinas/metabolismo , Oligopeptídeos/química , Animais , Cálcio/metabolismo , Quelantes de Cálcio/química , Gadolínio/química , Integrinas/química , Imageamento por Ressonância Magnética , Magnetismo , Masculino , Microscopia de Fluorescência , Oligopeptídeos/síntese química , Oligopeptídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/diagnóstico por imagem
20.
Int J Mol Sci ; 22(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921510

RESUMO

Rare diseases affect a small part of the population, and the most affected are children. Because of the low availability of patients for testing, the pharmaceutical industry cannot develop drugs for the diagnosis of many of these orphan diseases. In this sense, the use of benzothiazole compounds that are highly selective and can act as spectroscopy probes, especially the compound 2-(4'-aminophenyl)benzothiazole (ABT), has been highlighted. This article reports the design of potential contrast agents based on ABT and iron to develop a new material with an efficient mechanism to raise the relaxation rate, facilitating diagnosis. The ABT/δ-FeOOH hybrid material was prepared by grafting (N-(4'-aminophenyl) benzothiazole-2-bromoacetamide) on the surface of the iron oxyhydroxide particles. FTIR spectra confirmed the material formations of the hybrid material ABT/δ-FeOOH. SEM analysis checked the covering of nanoflakes' surfaces in relation to the morphology of the samples. The theoretical calculations test a better binding mode of compound with iron oxyhydroxide. Theoretical findings show the radical capture mechanism in the stabilization of this new material. In this context, Fe3+ ions are an electron acceptor from the organic phase.


Assuntos
Benzotiazóis/química , Meios de Contraste/uso terapêutico , Compostos Férricos/química , Doenças Raras/diagnóstico , Meios de Contraste/química , Humanos , Íons/química , Ferro/química , Fenômenos Magnéticos , Doenças Raras/diagnóstico por imagem , Doenças Raras/patologia , Análise Espectral
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...