RESUMO
ProGlo is an efficient steroid receptor-targeted magnetic resonance (MR) imaging contrast agent (CA). It has been shown to bind to the progesterone receptor (PR) and produce enhanced image contrast in PR-positive cells and tissues in vitro and in vivo. However, the hydrophobicity of the steroid targeting domain of ProGlo (logP = 1.4) limits its formulation and delivery at clinically relevant doses. In this work, a hydrophobic moiety was utilized to drive efficient adsorption onto nanodiamond (ND) clusters to form a water-soluble nanoconstruct (logP = -2.4) with 80% release in 8 h under biological conditions. In cell culture, the ND-ProGlo construct delivered increased concentrations of ProGlo to target cells compared to ProGlo alone. Importantly, these results were accomplished without the use of solvents such as DMSO, providing a significant advance toward formulating ProGlo for translational applications. Biodistribution studies confirm the delivery of ProGlo to PR(+) tissues with enhanced efficacy over untargeted controls. These results demonstrate the potential for a noncovalent ND-CA construct as a general strategy for solubilizing and delivering hydrophobic targeted MR CAs.
Assuntos
Neoplasias da Mama/patologia , Meios de Contraste/farmacocinética , Imageamento por Ressonância Magnética/métodos , Nanoconjugados/química , Nanodiamantes/administração & dosagem , Receptores de Progesterona/metabolismo , Animais , Neoplasias da Mama/metabolismo , Meios de Contraste/química , Feminino , Humanos , Camundongos , Nanodiamantes/química , Receptores de Progesterona/química , Solubilidade , Distribuição Tecidual , Células Tumorais CultivadasRESUMO
We describe a new, and vastly superior approach for labeling spherical nucleic acid conjugates (SNAs) with diagnostic probes. SNAs have been shown to provide the unique ability to traverse the cell membrane and deliver surface conjugated DNA into cells while preserving the DNA from nuclease degradation. Our previous work on preparing diagnostically labeled SNAs was labor intensive, relatively low yielding, and costly. Here, we describe a straightforward and facile preparation for labeling SNAs with optical and MR imaging probes with significantly improved physical properties. The synthesis of Gd(III) labeled DNA Au nanoparticle conjugates is achieved by sequential conjugation of 3'-thiol-modified oligonucleotides and cofunctionalization of the particle surface with the subsequent addition of 1,2 diothiolate modified chelates of Gd(III) (abbreviated: DNA-GdIII@AuNP). This new generation of SNA conjugates has a 2-fold increase of DNA labeling and a 1.4-fold increase in Gd(III) loading compared to published constructs. Furthermore, the relaxivity ( r1) is observed to increase 4.5-fold compared to the molecular dithiolane-Gd(III) complex, and 1.4-fold increase relative to previous particle constructs where the Gd(III) complexes were conjugated to the oligonucleotides rather than directly to the Au particle. Importantly, this simplified approach (2 steps) exploits the advantages of previous Gd(III) labeled SNA platforms; however, this new approach is scalable and eliminates modification of DNA for attaching the contrast agent, and the particles exhibit improved cell labeling.
Assuntos
DNA/química , Ouro/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas Metálicas/química , Sondas Moleculares/química , Meios de Contraste , Gadolínio/química , Compostos de Sulfidrila/química , Propriedades de SuperfícieRESUMO
In vivo cell tracking is vital for understanding migrating cell populations, particularly cancer and immune cells. Magnetic resonance (MR) imaging for long-term tracking of transplanted cells in live organisms requires cells to effectively internalize Gd(III) contrast agents (CAs). Clinical Gd(III)-based CAs require high dosing concentrations and extended incubation times for cellular internalization. To combat this, we have devised a series of Gd(III)-gold nanoconjugates (Gd@AuNPs) with varied chelate structure and nanoparticle-chelate linker length, with the goal of labeling and imaging breast cancer cells. These new Gd@AuNPs demonstrate significantly enhanced labeling compared to previous Gd(III)-gold-DNA nanoconstructs. Variations in Gd(III) loading, surface packing, and cell uptake were observed among four different Gd@AuNP formulations suggesting that linker length and surface charge play an important role in cell labeling. The best performing Gd@AuNPs afforded 23.6 ± 3.6 fmol of Gd(III) per cell at an incubation concentration of 27.5 µM-this efficiency of Gd(III) payload delivery (Gd(III)/cell normalized to dose) exceeds that of previous Gd(III)-Au conjugates and most other Gd(III)-nanoparticle formulations. Further, Gd@AuNPs were well-tolerated in vivo in terms of biodistribution and clearance, and supports future cell tracking applications in whole-animal models.
Assuntos
Gadolínio/química , Ouro/química , Imageamento por Ressonância Magnética/métodos , Nanoconjugados/química , Animais , Linhagem Celular Tumoral , Humanos , Espectrometria de Massas , CamundongosRESUMO
Pancreatic adenocarcinoma has a 5 year survival of approximately 3% and median survival of 6 months and is among the most dismal of prognoses in all of medicine. This poor prognosis is largely due to delayed diagnosis where patients remain asymptomatic until advanced disease is present. Therefore, techniques to allow early detection of pancreatic adenocarcinoma are desperately needed. Imaging of pancreatic tissue is notoriously difficult, and the development of new imaging techniques would impact our understanding of organ physiology and pathology with applications in disease diagnosis, staging, and longitudinal response to therapy in vivo. Magnetic resonance imaging (MRI) provides numerous advantages for these types of investigations; however, it is unable to delineate the pancreas due to low inherent contrast within this tissue type. To overcome this limitation, we have prepared a new Gd(III) contrast agent that accumulates in the pancreas and provides significant contrast enhancement by MR imaging. We describe the synthesis and characterization of a new dithiolane-Gd(III) complex and a straightforward and scalable approach for conjugation to a gold nanoparticle. We present data that show the nanoconjugates exhibit very high per particle values of r1 relaxivity at both low and high magnetic field strengths due to the high Gd(III) payload. We provide evidence of pancreatic tissue labeling that includes MR images, post-mortem biodistribution analysis, and pancreatic tissue evaluation of particle localization. Significant contrast enhancement was observed allowing clear identification of the pancreas with contrast-to-noise ratios exceeding 35:1.
Assuntos
Meios de Contraste/química , Gadolínio/química , Ouro/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas Metálicas/química , Neoplasias Pancreáticas/diagnóstico por imagem , Compostos de Sulfidrila/química , Animais , Gadolínio/farmacocinética , Xenoenxertos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Nanoconjugados/química , Tamanho da Partícula , Propriedades de Superfície , Distribuição Tecidual , Neoplasias PancreáticasRESUMO
The ability to track labeled cancer cells in vivo would allow researchers to study their distribution, growth, and metastatic potential within the intact organism. Magnetic resonance (MR) imaging is invaluable for tracking cancer cells in vivo as it benefits from high spatial resolution and the absence of ionizing radiation. However, many MR contrast agents (CAs) required to label cells either do not significantly accumulate in cells or are not biologically compatible for translational studies. We have developed carbon-based nanodiamond-gadolinium(III) aggregates (NDG) for MR imaging that demonstrated remarkable properties for cell tracking in vivo. First, NDG had high relaxivity independent of field strength, a finding unprecedented for gadolinium(III) [Gd(III)]-nanoparticle conjugates. Second, NDG demonstrated a 300-fold increase in the cellular delivery of Gd(III) compared to that of clinical Gd(III) chelates without sacrificing biocompatibility. Further, we were able to monitor the tumor growth of NDG-labeled flank tumors by T1- and T2-weighted MR imaging for 26 days in vivo, longer than was reported for other MR CAs or nuclear agents. Finally, by utilizing quantitative maps of relaxation times, we were able to describe tumor morphology and heterogeneity (corroborated by histological analysis), which would not be possible with competing molecular imaging modalities.
Assuntos
Gadolínio , Imagem Molecular , Nanodiamantes , Neoplasias Experimentais/diagnóstico por imagem , Animais , Meios de Contraste , Feminino , Imageamento por Ressonância Magnética , Camundongos , Camundongos SCIDRESUMO
Calcium [Ca(II)] is a fundamental transducer of electrical activity in the central nervous system (CNS). Influx of Ca(II) into the cytosol is responsible for action potential initiation and propagation, and initiates interneuronal communication via release of neurotransmitters and activation of gene expression. Despite the importance of Ca(II) in physiology, it remains a challenge to visualize Ca(II) flux in the central nervous system (CNS) in vivo. To address these challenges, we have developed a new generation, Ca(II)-activated MRI contrast agent that utilizes ethyl esters to increase cell labeling and prevent extracellular divalent Ca(II) binding. Following labeling, the ethyl esters can be cleaved, thus allowing the agent to bind Ca(II), increasing relaxivity and resulting in enhanced positive MR image contrast. The ability of this probe to discriminate between extra- and intracellular Ca(II) may allow for spatiotemporal in vivo imaging of Ca(II) flux during seizures or ischemia where large Ca(II) fluxes (1-10 µM) can result in cell death.
Assuntos
Cálcio/análise , Meios de Contraste/metabolismo , Esterases/metabolismo , Imageamento por Ressonância Magnética , Animais , Cálcio/metabolismo , Linhagem Celular , Permeabilidade da Membrana Celular , Meios de Contraste/química , Meios de Contraste/farmacocinética , Espaço Extracelular/química , Espaço Extracelular/metabolismo , Hipocampo/citologia , Hipocampo/metabolismo , Espaço Intracelular/química , Espaço Intracelular/metabolismo , Imageamento por Ressonância Magnética/métodos , CamundongosRESUMO
Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging.
Assuntos
Quelantes/química , Corantes/química , Meios de Contraste/química , Gadolínio/química , Imageamento por Ressonância Magnética , Imagem Multimodal , Imagem Óptica , Animais , Quelantes/síntese química , Quelantes/farmacocinética , Corantes/síntese química , Corantes/farmacocinética , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Feminino , Gadolínio/farmacocinética , Humanos , Raios Infravermelhos , Células MCF-7 , Camundongos Nus , Neoplasias/diagnóstico , Distribuição TecidualRESUMO
Nanodiscs are monodisperse, self-assembled discoidal particles that consist of a lipid bilayer encircled by membrane scaffold proteins (MSP). Nanodiscs have been used to solubilize membrane proteins for structural and functional studies and deliver therapeutic phospholipids. Herein, we report on tetramethylrhodamine (TMR) tagged nanodiscs that solubilize lipophilic MR contrast agents for generation of multimodal nanoparticles for cellular imaging. We incorporate both multimeric and monomeric Gd(III)-based contrast agents into nanodiscs and show that particles containing the monomeric agent (ND2) label cells with high efficiency and generate significant image contrast at 7 T compared to nanodiscs containing the multimeric agent (ND1) and Prohance, a clinically approved contrast agent.
Assuntos
Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Nanoestruturas/química , Imagem Óptica/métodos , Meios de Contraste/química , Gadolínio/química , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Rodaminas/química , SolubilidadeRESUMO
Long-term cell tracking using MR imaging necessitates the development of contrast agents that both label and are retained by cells. One promising strategy for long-term cell labeling is the development of lipophilic Gd(III)-based contrast agents that anchor into the cell membrane. We have previously reported the efficacy of monomeric and multimeric lipophilic agents and showed that the monomeric agents have improved labeling and contrast enhancement of cell populations. Here, we report on the synthesis, characterization, and in vitro testing of a series of monomeric lipophilic contrast agents with varied alkyl chain compositions. We show that these agents disperse in water, localize to the cell membrane, and label HeLa and MCF7 cells effectively. Additionally, these agents have up to tenfold improved retention in cells compared to clinically available ProHance(®).
Assuntos
Membrana Celular/metabolismo , Meios de Contraste/síntese química , Complexos de Coordenação/síntese química , Gadolínio/química , Membrana Celular/química , Meios de Contraste/toxicidade , Complexos de Coordenação/toxicidade , Gadolínio/toxicidade , Células HeLa , Humanos , Células MCF-7 , Imageamento por Ressonância MagnéticaRESUMO
Cell tracking in vivo with MR imaging requires the development of contrast agents with increased sensitivity that effectively label and are retained by cells. Most clinically approved Gd(III)-based contrast agents require high incubation concentrations and prolonged incubation times for cellular internalization. Strategies to increase contrast agent permeability have included conjugating Gd(III) complexes to cell penetrating peptides, nanoparticles, and small molecules which have greatly improved cell labeling but have not resulted in improved cellular retention. To overcome these challenges, we have synthesized a series of lipophilic Gd(III)-based MR contrast agents that label cell membranes in vitro. Two of the agents were synthesized with a multiplexing strategy to contain three Gd(III) chelates (1 and 2) while the third contains a single Gd(III) chelate (3). These new agents exhibit significantly enhanced labeling and retention in HeLa and MDA-MB-231-mcherry cells compared to agents that are internalized by cells (4 and Prohance).
Assuntos
Membrana Celular/química , Meios de Contraste/química , Gadolínio/química , Imageamento por Ressonância Magnética , Compostos Organometálicos/química , Animais , Linhagem Celular Tumoral , Proliferação de Células , Células HeLa , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Modelos Moleculares , Estrutura Molecular , Células NIH 3T3 , Compostos Organometálicos/síntese química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Determination of progesterone receptor (PR) status in hormone-dependent diseases is essential in ascertaining disease prognosis and monitoring treatment response. The development of a noninvasive means of monitoring these processes would have significant impact on early detection, cost, repeated measurements, and personalized treatment options. Magnetic resonance imaging (MRI) is widely recognized as a technique that can produce longitudinal studies, and PR-targeted MR probes may address a clinical problem by providing contrast enhancement that reports on PR status without biopsy. Commercially available MR contrast agents are typically delivered via intravenous injection, whereas steroids are administered subcutaneously. Whether the route of delivery is important for tissue accumulation of steroid-modified MRI contrast agents to PR-rich tissues is not known. To address this question, modification of the chemistry linking progesterone with the gadolinium chelate led to MR probes with increased water solubility and lower cellular toxicity and enabled administration through the blood. This attribute came at a cost through lower affinity for PR and decreased ability to cross the cell membrane, and ultimately it did not improve delivery of the PR-targeted MR probe to PR-rich tissues or tumors in vivo. Overall, these studies are important, as they demonstrate that targeted contrast agents require optimization of delivery and receptor binding of the steroid and the gadolinium chelate for optimal translation in vivo.
Assuntos
Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Progesterona/química , Receptores de Progesterona/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/efeitos adversos , Meios de Contraste/metabolismo , Feminino , Humanos , Camundongos , Octanóis/química , Progesterona/efeitos adversos , Progesterona/metabolismo , Solubilidade , Água/químicaRESUMO
Polymeric biomedical implants are an important clinical tool, but degradation remains difficult to determine post-implantation. Computed tomography (CT) could be a powerful tool for device monitoring, but polymers require incorporation of radiopaque contrast agents to be distinguishable from tissue. In addition, immune response to radiopaque devices must be characterized as it modulates device function. Radiopaque devices and films were produced by incorporating 0-20 wt% TaOx nanoparticles into polymers: polycaprolactone (PCL) and poly(lactide-co-glycolide) (PLGA). In vitro inflammatory responses of mouse bone marrow-derived macrophages to polymer matrix incorporating TaOx nanoparticles was determined by monitoring cytokine secretion. Nanoparticle addition stimulated a slight inflammatory reaction, increasing TNFα secretion, mediated by changes in polymer matrix properties. Subsequently, devices (PLGA 50:50 + 20 wt% TaOx) were implanted subcutaneously in a mouse model of chronic inflammation, that featured a sustained increase in inflammatory response local to the implant site over 12 weeks. No changes to device degradation rates or foreign body response were noted between a normal and chronically stimulated inflammatory environment. Serial CT device monitoring post-implantation provided a detailed timeline of device collapse, with no rapid, spontaneous release of nanoparticles that occluded matrix visualization. Importantly, repeat CT sessions did not ablate the immune system or alter degradation kinetics. Thus, polymer devices incorporating radiopaque nanoparticles can be used for in situ monitoring and be readily combined with other medical imaging techniques, for a dynamic view biomaterial and tissue interactions. STATEMENT OF SIGNIFICANCE: A growing number of implantable devices are in use in the clinic, exposing patients to inherent risks of implant movement, collapse, and infection. The ability to monitor implanted devices would enable faster diagnosis of failure and open the door for personalized rehabilitation therapies - both of which could vastly improve patient outcomes. Unfortunately, polymeric materials which make up most biomedical devices are not radiologically distinguishable from tissue post-implantation. The introduction of radiopaque nanoparticles into polymers allows for serial monitoring via computed tomography, without affecting device degradation. Here we demonstrate for the first time that nanoparticles do not undergo burst release from devices post-implantation and that inflammatory responses - a key determinant of device function in vivo - are also unaffected by nanoparticle addition.
Assuntos
Meios de Contraste , Inflamação , Microtomografia por Raio-X , Animais , Inflamação/patologia , Camundongos , Meios de Contraste/química , Meios de Contraste/farmacocinética , Poliésteres/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Macrófagos/metabolismo , Nanopartículas/química , Camundongos Endogâmicos C57BLRESUMO
We report the structural optimization and mechanistic investigation of a series of bioactivated magnetic resonance imaging contrast agents that transform from low relaxivity to high relaxivity in the presence of Zn(II). The change in relaxivity results from a structural transformation of the complex that alters the coordination environment about the Gd(III) center. Here, we have performed a series of systematic modifications to determine the structure that provides the optimal change in relaxivity in response to the presence of Zn(II). Relaxivity measurements in the presence and absence of Zn(II) were used in conjunction with measurements regarding water access (namely, number of water molecules bound) to the Gd(III) center and temperature-dependent (13)C NMR spectroscopy to determine how the coordination environment about the Gd(III) center is affected by the distance between the Zn(II)-binding domain and the Gd(III) chelate, the number of functional groups on the Zn(II)-binding domain, and the presence of Zn(II). The results of this study provide valuable insight into the design principles for future bioactivated magnetic resonance probes.
Assuntos
Meios de Contraste/química , Gadolínio/química , Imageamento por Ressonância Magnética/métodos , Zinco/química , Quelantes/química , Técnicas de Química Sintética , Espectroscopia de Ressonância Magnética/métodos , Relação Estrutura-Atividade , TemperaturaRESUMO
A bacteria-targeted MR contrast agent, Zn-1, consisting of two Zn-dipicolylamine (Zn-dpa) groups conjugated to a GdIII chelate has been synthesized and characterized. In vitro studies with S. aureus and E. coli show that Zn-1 exhibits a significant improvement in bacteria labeling efficiency vs. control. Studies with a structural analogue, Zn-2, indicate that removal of one Zn-dpa moiety dramatically reduces the agent's affinity for bacteria. The ability of Zn-1 to significantly reduce the T1 of labeled vs. unlabeled bacteria, resulting in enhanced MR image contrast, demonstrates its potential for visualizing bacterial infections in vivo.
RESUMO
Faster, more sensitive, and higher resolution quantitative instrumentation are aiding a deeper understanding of how inorganic chemistry regulates key biological processes. Researchers can now image and quantify metals with subcellular resolution, leading to a vast array of new discoveries in organismal development, pathology, and disease. Metals have recently been implicated in several diseases such as Parkinson's, Alzheimers, ischemic stroke, and colorectal cancer that would not be possible without these advancements. In this review, instead of focusing on instrumentation we focus on recent applications of label-free elemental imaging and quantification and how these tools can lead to a broader understanding of metals role in systems biology and human pathology.
Assuntos
Diagnóstico por Imagem , Metais , Diagnóstico por Imagem/métodos , Humanos , Íons , Espectrometria de Massas/métodosRESUMO
In vivo iron load must be monitored to prevent complications from iron overload diseases such as hemochromatosis or transfusion-dependent anemias. While liver biopsy is the gold standard for determining in vivo iron load, MRI offers a noninvasive approach. MR phantoms have been reported that estimate iron concentration in the liver and mimic relaxation characteristics of in vivo deposits of hemosiderin. None of these phantoms take into account the size distribution of hemosiderin, which varies from patient to patient based on iron load. We synthesized stable and reproducible microsphere-ferritin conjugates (ferribeads) of different sizes that are easily characterized for several parameters that are necessary for modeling such as iron content and bead fraction. T(1) s and T(2) s were measured on a 1.41-T low-resolution NMR spectrometer and followed a size-dependent trend. Ferribeads imaged at 4.7 and 14.1 T showed that signal intensities are dependent on the distribution of ferritin around the bead rather than the iron concentration alone. These particles can be used to study the effects of particle size, ferritin distribution, and bead fraction on proton relaxation and may be of use in mimicking hemosiderin in a phantom for estimating iron concentration.
Assuntos
Ferritinas , Imageamento por Ressonância Magnética , Microesferas , Poliestirenos , Materiais Revestidos Biocompatíveis/química , Ferritinas/química , Imageamento por Ressonância Magnética/métodos , Magnetismo , Tamanho da Partícula , Imagens de Fantasmas , Poliestirenos/químicaRESUMO
Progesterone receptor (PR) is strongly associated with disease prognosis and therapeutic efficacy in hormone-related diseases such as endometriosis and breast, ovarian, and uterine cancers. Receptor status is currently determined by immunohistochemistry assays. However, noninvasive PR imaging agents could improve disease detection and help elucidate pathological molecular pathways, leading to new therapies and animal disease models. A series of water-soluble PR-targeted magnetic resonance imaging (MRI) probes were synthesized using Cu(I)-catalyzed click chemistry and evaluated in vitro and in vivo. These agents demonstrated activation of PR in vitro and preferential accumulation in PR(+) compared to PR(-) human breast cancer cells with low toxicity. In xenograft tumor models, the agents demonstrated enhanced signal intensity in PR(+) tumors compared to PR(-) tumors. The results suggest that these agents may be promising MRI probes for PR(+) diseases.
Assuntos
Meios de Contraste/química , Meios de Contraste/síntese química , Imageamento por Ressonância Magnética/métodos , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Progesterona/química , Água/química , Animais , Azidas/síntese química , Azidas/química , Azidas/metabolismo , Química Click/métodos , Meios de Contraste/metabolismo , Európio/química , Feminino , Gadolínio/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Transplante de Neoplasias , Neoplasias Experimentais/diagnóstico , Progesterona/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismoRESUMO
Progesterone receptor (PR) is a significant biomarker in diseases such as endometriosis and breast, ovarian, and uterine cancers that is associated with disease prognosis and therapeutic efficacy. While receptor status is currently determined by immunohistochemistry assays, the development of noninvasive PR imaging agents could improve molecular characterization, treatment decisions, and disease monitoring. ProGlo, a progesterone-conjugated magnetic resonance imaging (MRI) contrast agent, was evaluated in vivo to determine whether it targets and enhances signal intensity in organs and tumors that express high PR levels. A tissue distribution study indicated that ProGlo accumulates in the PR-rich uterus, which was confirmed by in vivo imaging studies. Ex vivo images of these organs revealed that ProGlo was distributed in the substructures that express high PR levels. In xenograft tumor models, ProGlo was taken up to a greater extent than the nonfunctionalized Gd-DO3A in tumors, particularly in PR(+) tumors. The ability to accumulate and enhance signal intensity in PR(+) organs and tumors suggests that ProGlo may be a promising MRI probe for PR(+) diseases.
Assuntos
Neoplasias da Mama/patologia , Meios de Contraste/química , Imageamento por Ressonância Magnética/métodos , Receptores de Progesterona/metabolismo , Esteroides/química , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Molecular/métodosRESUMO
A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized, enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles significantly reduced the T(1) of water protons with a per-Gd(III) relaxivity of 58.82 +/- 1.18 mM(-1) s(-1) at 1.5 T (60 MHz). This represents a 10-fold increase compared to the monomer Gd(III) complex (r(1) = 5.42 +/- 0.20 mM(-1) s(-1)) and is among the highest per-Gd(III) relaxivities reported.
Assuntos
Meios de Contraste/farmacologia , Gadolínio/química , Imageamento por Ressonância Magnética/métodos , Nanomedicina/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Animais , Calorimetria/métodos , Diamante , Células HeLa , Humanos , Camundongos , Microscopia Eletrônica de Transmissão/métodos , Conformação Molecular , Células NIH 3T3RESUMO
Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date 1,2 . In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.