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1.
Molecules ; 25(24)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371284

RESUMO

Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer's disease, or cardiovascular diseases. Among all the available PET-active radionuclides, 18F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t1/2 = 109.77 min; 97% ß+ emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies.


Assuntos
Corantes Fluorescentes/administração & dosagem , Radioisótopos de Flúor/administração & dosagem , Imagem Molecular/métodos , Imagem Óptica/métodos , Animais , Doença , Fluorescência , Humanos , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem
2.
Int J Mol Sci ; 21(24)2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33339139

RESUMO

There are many nanoencapsulation systems available today. Among all these, mesoporous silica particles (MSPs) have received great attention in the last few years. Their large surface-to-volume ratio, biocompatibility, and versatility allow the encapsulation of a wide variety of drugs inside their pores. However, their chemical instability in biological fluids is a handicap to program the precise release of the therapeutic compounds. Taking advantage of the dissolving capacity of silica, in this study, we generate hollow capsules using MSPs as transitory sacrificial templates. We show how, upon MSP coating with different polyelectrolytes or proteins, fully customized hollow shells can be produced. These capsules are biocompatible, flexible, and biodegradable, and can be decorated with nanoparticles or carbon nanotubes to endow the systems with supplementary intrinsic properties. We also fill the capsules with a fluorescent dye to demonstrate intracellular compound release. Finally, we document how fluorescent polymeric capsules are engulfed by cells, releasing their encapsulated agent during the first 96 h. In summary, here, we describe how to assemble a highly versatile encapsulation structure based on silica mesoporous cores that are completely removed from the final polymeric capsule system. These drug encapsulation systems are highly customizable and have great versatility as they can be made using silica cores of different sizes and multiple coatings. This provides capsules with unique programmable attributes that are fully customizable according to the specific needs of each disease or target tissue for the development of nanocarriers in personalized medicine.


Assuntos
Nanocápsulas/química , Dióxido de Silício/química , Liberação Controlada de Fármacos , Corantes Fluorescentes/administração & dosagem , Células HeLa , Humanos , Polieletrólitos/química
3.
J Glaucoma ; 29(11): 1006-1016, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32947358

RESUMO

PURPOSE: To quantify aerosol and droplets generated during noncontact tonometry (NCT) and assess the spread distance of the same. METHODOLOGY: This was an experimental study on healthy human volunteers (n=8 eyes). In an experimental setup, NCT was performed on eyes (n=8) of human volunteers under normal settings, with a single and 2 drops of lubricant. High-speed shadowgraphy, frontal lighting technique, and fluorescein analysis were used to detect the possible generation of any droplets and aerosols. Mathematical computation of the spread of the droplets was then performed. RESULTS: In a natural setting, there was no droplet or aerosol production. Minimal splatter along with droplet ejection was observed when 1 drop of lubricant was used before NCT. When 2 drops of lubricant were instilled, a significant amount of fluid ejection in the form of a sheet that broke up into multiple droplets was observed. Some of these droplets traversed back to the tonometer. Droplets ranging from 100 to 500 µm in diameter were measured. CONCLUSIONS: There was no droplet generation during NCT performed in a natural setting. However, NCT should be avoided in conditions with high-tear volume (natural or artificial) as it would lead to droplet spread and tactile contamination.


Assuntos
Aerossóis/química , Betacoronavirus , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pressão Intraocular/fisiologia , Pneumonia Viral/transmissão , Lágrimas/química , Tonometria Ocular/instrumentação , Adolescente , Adulto , Monitoramento Ambiental , Feminino , Fluoresceína/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Humanos , Lubrificantes Oftálmicos/administração & dosagem , Masculino , Imagem Óptica , Pandemias , Adulto Jovem
4.
Nat Commun ; 11(1): 3111, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32561725

RESUMO

Midbrain dopaminergic (DA) axons make long longitudinal projections towards the striatum. Despite the importance of DA striatal innervation, processes involved in establishment of DA axonal connectivity remain largely unknown. Here we demonstrate a striatal-specific requirement of transcriptional regulator Nolz1 in establishing DA circuitry formation. DA projections are misguided and fail to innervate the striatum in both constitutive and striatal-specific Nolz1 mutant embryos. The lack of striatal Nolz1 expression results in nigral to pallidal lineage conversion of striatal projection neuron subtypes. This lineage switch alters the composition of secreted factors influencing DA axonal tract formation and renders the striatum non-permissive for dopaminergic and other forebrain tracts. Furthermore, transcriptomic analysis of wild-type and Nolz1-/- mutant striatal tissue led to the identification of several secreted factors that underlie the observed guidance defects and proteins that promote DA axonal outgrowth. Together, our data demonstrate the involvement of the striatum in orchestrating dopaminergic circuitry formation.


Assuntos
Orientação de Axônios/fisiologia , Axônios/fisiologia , Corpo Estriado/crescimento & desenvolvimento , Neurônios Dopaminérgicos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Animais , Carbocianinas/administração & dosagem , Corpo Estriado/diagnóstico por imagem , Embrião de Mamíferos , Feminino , Corantes Fluorescentes/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/genética , Microscopia Intravital , Camundongos Knockout , Técnicas Analíticas Microfluídicas , Microinjeções , Microscopia Confocal , Rede Nervosa/fisiologia , Proteínas do Tecido Nervoso/genética , Técnicas de Cultura de Tecidos
5.
J Surg Res ; 253: 280-287, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402853

RESUMO

BACKGROUND: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. METHODS: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH. RESULTS: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm2versus 1.4 ± 1.5 mm2, respectively, P = 0.045) and medial area (5.1 ± 1.9 mm2versus 2.7 ± 2.4 mm2, respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. CONCLUSIONS: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.


Assuntos
Artérias Carótidas/cirurgia , Neointima/prevenção & controle , Fotoquimioterapia/métodos , Veia Safena/transplante , Enxerto Vascular/métodos , Túnica Adventícia/efeitos dos fármacos , Túnica Adventícia/efeitos da radiação , Animais , Colágeno/química , Colágeno/efeitos dos fármacos , Colágeno/efeitos da radiação , Feminino , Corantes Fluorescentes/administração & dosagem , Luz , Neointima/diagnóstico , Neointima/etiologia , Neointima/patologia , Rosa Bengala/administração & dosagem , Veia Safena/diagnóstico por imagem , Veia Safena/patologia , Suínos , Porco Miniatura , Transplante Autólogo/efeitos adversos , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Enxerto Vascular/efeitos adversos , Grau de Desobstrução Vascular
6.
Chem Commun (Camb) ; 56(28): 3999-4002, 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32154536

RESUMO

Novel red Zn(ii) complex-based fluorescent probes featuring cryptolepine-curcumin derivatives, namely, [Zn(BQ)Cl2] (BQ-Zn) and [Zn(BQ)(Cur)]Cl (BQCur-Zn), were developed for the simple and fluorescent label-free detection of apoptosis, an important biological process. The probes could synergistically promote mitochondrion-mediated apoptosis and enhance tumor therapeutic effects in vitro and vivo.


Assuntos
Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Curcumina/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Alcaloides Indólicos/administração & dosagem , Sondas Moleculares/administração & dosagem , Quinolinas/administração & dosagem , Zinco/administração & dosagem , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Fotoquimioterapia
7.
Nat Commun ; 11(1): 1250, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144257

RESUMO

Currently, there are no non-invasive tools to accurately diagnose wound and surgical site infections before they become systemic or cause significant anatomical damage. Fluorescence and photoacoustic imaging are cost-effective imaging modalities that can be used to noninvasively diagnose bacterial infections when paired with a molecularly targeted infection imaging agent. Here, we develop a fluorescent derivative of maltotriose (Cy7-1-maltotriose), which is shown to be taken up in a variety of gram-positive and gram-negative bacterial strains in vitro. In vivo fluorescence and photoacoustic imaging studies highlight the ability of this probe to detect infection, assess infection burden, and visualize the effectiveness of antibiotic treatment in E. coli-induced myositis and a clinically relevant S. aureus wound infection murine model. In addition, we show that maltotriose is an ideal scaffold for infection imaging agents encompassing better pharmacokinetic properties and in vivo stability than other maltodextrins (e.g. maltohexose).


Assuntos
Corantes Fluorescentes/administração & dosagem , Imagem Molecular/métodos , Miosite/diagnóstico por imagem , Infecção da Ferida Cirúrgica/diagnóstico por imagem , Trissacarídeos/administração & dosagem , Animais , Carbocianinas/administração & dosagem , Carbocianinas/química , Modelos Animais de Doenças , Estabilidade de Medicamentos , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Humanos , Injeções Intravenosas , Medições Luminescentes/métodos , Camundongos , Microscopia de Fluorescência/métodos , Sondas Moleculares/administração & dosagem , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Miosite/microbiologia , Técnicas Fotoacústicas/métodos , Ratos , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/metabolismo , Infecção da Ferida Cirúrgica/microbiologia , Trissacarídeos/química , Trissacarídeos/metabolismo
8.
J Vis Exp ; (156)2020 02 29.
Artigo em Inglês | MEDLINE | ID: mdl-32176204

RESUMO

In cases of cerebrospinal fluid (CSF) leaks, reliable detection of their origins is needed to seal the leak sufficiently and prevent complications, such as meningitis. A method is presented here using intrathecal administered fluorescein in a clinical case of bilateral congenital ear malformation. A fluorescent dye is administered intrathecally to achieve intraoperative visualization of CSF leaks. The dye is applied 20 min before surgery, and concentration of 5% is used. Per every 10 kg of body weight, 0.1 mL of the fluid is applied intrathecally. The fluorescein is visualized using a fully digital microscope. The origin of the fluid leak is identified in the stapes footplate. During primary surgery, it is sealed, and cochlea implantation is performed for hearing restoration. In this specific case, 6 weeks later, the implant was explanted due to acute meningitis, and the electrode array was left as a spacer. Postoperatively, in the aural smear, ß-transferrin was detected. During a revision mastoidectomy, dislocated coverage of the leak was found. The stapes was removed and oval window sealed. Five days after revision surgery, no ß-transferrin was detected in the aural smear. During the revision of cochlea implantation 6 months later, intact coverage of the oval niche was observed. Thus, intrathecal fluorescein application proves to be a reliable tool for the detection of CSF leaks. It facilitates the orientation in malformations and complicated or unknown surgical situs. In the literature, its use is described for CSF fistulas in endonasal surgery but is rarely described in skull base and mastoid surgeries. The method has been used successfully in several cases with CSF leaks, and the results confirm the feasibility of safely accessing the origin of the leak.


Assuntos
Vazamento de Líquido Cefalorraquidiano/diagnóstico , Cóclea/anormalidades , Corantes Fluorescentes/administração & dosagem , Protocolos Clínicos , Cóclea/cirurgia , Fluoresceína , Humanos , Lactente , Injeções Espinhais , Nariz/lesões , Estudos Retrospectivos , Estribo/metabolismo , Estribo/ultraestrutura
9.
Biomater Sci ; 8(8): 2308-2317, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32186291

RESUMO

Overlapping substrate specificities within the family of matrix metalloproteinases (MMPs), usually caused by their highly conserved structural topology, increase the potential for a substrate to be cleaved by multiple enzymes within this family, which leads to the decrease in the selectivity of MMP substrate-based probes. To resolve this issue, MT1-MMP activatable fluorogenic probes for tumor detection with enhanced specificity were developed by combining a fluorescence resonance energy transfer (FRET) peptide substrate and its specific binding peptide with different lengths of linkers. The specificity of the probes increased profiting from the high affinity of the MT1-MMP specific binding peptide while keeping the ability to amplify the output imaging signals in response to MMP activity with the FRET substrate. Enzyme kinetics analysis clearly demonstrated that the conjugation of P-1 and MT1-AF7p enhanced both the specificity and selectivity of the fluorogenic probes for MT1-MMP, and introducing a linker composed of 12 PEG subunits into these two fragments led to optimized specificity and selectivity of the fluorogenic probe for MT1-MMP. Both in vitro and in vivo results revealed that the imaging probe with the linker composed of 12 PEG subunits based on our designed strategy could be effectively applied for MT1-MMP positive tumor imaging. Since this strategy for enhancing the specificity of protease sensing probes can be applied to other proteases and is not just limited to MT1-MMP, it is an appealing platform to achieve selective tumor imaging.


Assuntos
Corantes Fluorescentes/administração & dosagem , Metaloproteinase 14 da Matriz/administração & dosagem , Peptídeos/administração & dosagem , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Humanos , Metaloproteinase 14 da Matriz/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Peptídeos/química , Proteínas Recombinantes/administração & dosagem
10.
J Surg Res ; 252: 16-21, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32217350

RESUMO

BACKGROUND: Tumor-associated glycoprotein (TAG)-72 is a pancarcinoma antigen that is overexpressed in greater than 80% of colorectal adenocarcinomas. CC49 is a TAG-72-specific antibody. The aim of the present study was to demonstrate selective imaging of colon tumors and metastases with the humanized TAG-72 antibody (anti-huCC49) conjugated to a near-infrared fluorophore in orthotopic mouse models. METHODS: Anti-huCC49 was conjugated to near-infrared dye IR800CW. Mouse imaging was performed with the Pearl Trilogy Small Animal and FLARE Imaging Systems. Subcutaneous mouse models of colon cancer cell line LS174T were used to determine the optimal dose of administration and timing of imaging. Orthotopic mouse models of LS174T were established by surgical orthotopic implantation of LS174T tumors onto the serosa of the cecum. Peritoneal carcinomatosis models were established by injection of LS174T cells into the peritoneum of nude mice. Mice were administered anti-huCC49-IR800 via tail vein injection. Mice were euthanized 72 h later and imaged after laparotomy. RESULTS: Subcutaneous LS174T xenografts demonstrated optimal tumor detection 72 h after administration with 50 µg anti-huCC49-IR800CW. Tumors were visualized with fluorescence imaging with a mean tumor-to-liver ratio of 7.39 (standard deviation: 2.76). In the orthotopic model, metastases smaller than 1 mm were fluorescently visualized that were invisible with bright light. CONCLUSIONS: Anti-huCC49-IR800CW provides sensitive and specific imaging of colon cancer and metastases at a submillimeter resolution in metastatic nude mice models. This provides a promising near-infrared probe for the imaging of colon cancer and metastases for preoperative diagnosis and fluorescence-guided surgery.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Antígenos de Neoplasias/imunologia , Neoplasias do Colo/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Ácidos Alcanossulfônicos/administração & dosagem , Ácidos Alcanossulfônicos/química , Animais , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Antineoplásicos/química , Anticorpos Antineoplásicos/imunologia , Linhagem Celular Tumoral , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/química , Imunoconjugados/imunologia , Indóis/administração & dosagem , Indóis/química , Camundongos , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Cuidados Pré-Operatórios/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cirurgia Assistida por Computador/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Microvasc Res ; 130: 103990, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32088162

RESUMO

BACKGROUND: Assessment of the coronary microcirculation remains challenging. OBJECTIVE: we explored the feasibility of evaluating the coronary microvasculature in rats with myocardial infarction (MI) using a three-dimensional visualization technique. METHODS: Animals were divided into the sham operation group (S), MI 45 min group (M45), and MI 180 min group (M180). Opened microvessels were labelled with the fluorescent dye DiI (1, 1'-dioctadecyl-3, 3, 3'3'-tetramethylindo carbocyanine perchlorate) using a heart perfusion method. The microvascular distribution and opening status were observed under laser scanning confocal microscopy, which was adjusted to facilitate evaluation of subjects around 6 to 20 µm. RESULTS: Microvascular vessels (6-20 µm) were successfully labelled by DiI. Intact and clear three-dimensional microvascular structures were observed in myocardium of sham rats and remote non-infarct myocardial tissue of MI rats, while there was almost no microvascular structure in the infarct area of the M45 group, and only a small amount of microvascular visualization was visualized in the infarct area of the M180 group. The microvascular area and microvascular density in M45 group and M180 group in the infarct border zone were significantly lower than corresponding area in S group. CONCLUSION: Three-dimensional visualization of opened coronary microvascular vessels is feasible in DiI-labelled myocardium in this rat MI model. This novel technique might be useful for defining the underlying mechanisms of coronary microvascular diseases and observe the efficacy of various therapy strategies on coronary microvessels.


Assuntos
Vasos Coronários/diagnóstico por imagem , Imageamento Tridimensional , Microscopia Confocal , Microscopia de Fluorescência , Microvasos/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem , Animais , Carbocianinas/administração & dosagem , Modelos Animais de Doenças , Estudos de Viabilidade , Corantes Fluorescentes/administração & dosagem , Valor Preditivo dos Testes , Ratos Sprague-Dawley
12.
Lab Anim (NY) ; 49(3): 79-88, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32042160

RESUMO

The intestinal immune system samples luminal contents to induce adaptive immune responses that include tolerance in the steady state and protective immunity during infection. How luminal substances are delivered to the immune system has not been fully investigated. Goblet cells have an important role in this process by delivering luminal substances to the immune system through the formation of goblet cell-associated antigen passages (GAPs). Soluble antigens in the intestinal lumen are transported across the epithelium transcellularly through GAPs and delivered to dendritic cells for presentation to T cells and induction of immune responses. GAPs can be identified and quantified by using the ability of GAP-forming goblet cells to take up fluorescently labeled dextran. Here, we describe a method to visualize GAPs and other cells that have the capacity to take up luminal substances by intraluminal injection of fluorescent dextran in mice under anesthesia, tissue sectioning for slide preparation and imaging with fluorescence microscopy. In contrast to in vivo two-photon imaging previously used to identify GAPs, this technique is not limited by anatomical constraints and can be used to visualize GAP formation throughout the length of the intestine. In addition, this method can be combined with common immunohistochemistry protocols to visualize other cell types. This approach can be used to compare GAP formation following different treatments or changes to the luminal environment and to uncover how sampling of luminal substances is altered in pathophysiological conditions. This protocol requires 8 working hours over 2-3 d to be completed.


Assuntos
Antígenos/metabolismo , Colo/imunologia , Células Dendríticas/imunologia , Células Caliciformes/imunologia , Vigilância Imunológica , Intestino Delgado/imunologia , Animais , Apresentação do Antígeno/efeitos dos fármacos , Antígenos/imunologia , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Dextranos/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Células Caliciformes/efeitos dos fármacos , Mucosa Intestinal/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Microbiota/imunologia , Ovalbumina/administração & dosagem , Projetos de Pesquisa
13.
Soft Matter ; 16(10): 2473-2479, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32043107

RESUMO

Oxidative stress, caused by the overproduction of reactive oxygen species (ROS), is often observed in degenerative and/or metabolic diseases, tumors, and inflamed tissues. Boronic acids are emerging as a unique class of responsive biomaterials targeting ROS because of their reactivity toward H2O2. Herein, we examine the oxidative reactivity of nanoparticles from a boronic acid-installed polycarbonate. The extent of oxidation under different concentrations of H2O2 was tracked by the change in fluorescence intensity of an encapsulated solvatochromic reporter dye, demonstrating their sensitivity to biologically-relevant concentrations of hydrogen peroxide. Oxidation-triggered particle destabilization, however, was shown to be highly dependent on the concentration of the final oxidized polymer product, and was only achieved if it fell below polymer critical micelle concentration. Our results indicate that these nanocarriers serve as an excellent dual pH/H2O2 responsive vehicle for drug delivery.


Assuntos
Ácidos Borônicos/química , Preparações de Ação Retardada/química , Nanopartículas/química , Cimento de Policarboxilato/química , Polímeros/química , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Oxazinas/administração & dosagem , Oxazinas/química , Oxirredução
14.
Pharm Dev Technol ; 25(4): 517-523, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31903821

RESUMO

To this day, the oral delivery of biomacromolecules remains a major developmentally-oriented challenge. A combinatorial approach was followed at this study, to formulate an efficient carrier for the in vitro delivery of a model macromolecule, fluorescein isothiocyanate-dextran 4 kDa (FD4). The model macromolecule was formulated in a self-assembling peptide hydrogel (ac-(RADA)4-CONH2), prior to deposition in a hydroxypropyl methylcellulose-phthalate (HPMCP)-based 3D-printed capsule. Loading of FD4 was investigated for potential alterations on the structural (AFM) and gelling properties of the peptide carrier. Thermal analysis and morphological properties of the 3D-printed capsules were assessed by TGA, DSC and microscopy studies. For the peptide hydrogel, similar release profiles of FD4 were recorded in simulated gastric fluid pH 1.2 and phosphate buffer saline pH 7.4, indicating the need for a structural barrier, to protect the peptide carrier from the acidic environment of the stomach. The pH responsive character of the HPMCP-based capsule was evidenced in the release profiles of FD4 in a sequence of release media, i.e. simulated gastric fluid pH 1.2, simulated intestinal fluid pH 6.8 and phosphate buffer saline pH 7.4. The results supported the combinatorial formulation approach as a promising system for the efficient oral delivery of biomacromolecules.


Assuntos
Preparações de Ação Retardada/química , Dextranos/administração & dosagem , Fluoresceína-5-Isotiocianato/análogos & derivados , Corantes Fluorescentes/administração & dosagem , Metilcelulose/análogos & derivados , Peptídeos/química , Cápsulas/química , Liberação Controlada de Fármacos , Fluoresceína-5-Isotiocianato/administração & dosagem , Hidrogéis/química , Concentração de Íons de Hidrogênio , Metilcelulose/química , Impressão Tridimensional
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 230: 118024, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31954359

RESUMO

Due to the high activity and difficult to transport of nitric oxide, the controlled release of nitric oxide has been a new trend in the research on the biological effect of nitric oxide. In this paper, a water-soluble and turn-on fluorescent NO donor Rh-NO was synthesized. Upon 525 nm irradiation, the fluorescence of the Rh-NO at 568 nm enhanced with the quantum yield (ΦF) of Rh-NO changing from 5.08% to 35.96%. The mechanism of NO releasing was proved by HRMS and the Dan. The releasing time of 6 min and the releasing yield of 0.61 proved the superiority of Rh-NO. Excellent cell activity above 80% of Rh-NO and Rh guaranteed that nitric oxide was released from Rh-NO in lysosome and zebrafishes successfully, which provided a good platform to understand the biological effects of nitric oxide in lysosomes.


Assuntos
Corantes Fluorescentes/farmacocinética , Lisossomos/metabolismo , Doadores de Óxido Nítrico/farmacocinética , Peixe-Zebra/metabolismo , Animais , Linhagem Celular , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/síntese química , Humanos , Óxido Nítrico/análise , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/síntese química , Imagem Óptica , Solubilidade , Água/química
16.
BMC Ophthalmol ; 20(1): 24, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931766

RESUMO

BACKGROUND: Radiation therapy (RT) is the treatment of choice in patients with low-grade ocular adenexal mucosa-associated lymphoid tissue lymphoma (OAML) and many of them experience post-RT dry eye with varying severity. The purpose of the present study was to investigate ocular effects of RT on meibomian glands and dry eye by directly visualizing structural changes. Secondly, we focused on the comparison of two groups of patients according to tumor location and radiation technique. METHODS: Sixty-four eyes with OAML of conjunctiva, orbit, lacrimal gland, or lacrimal sac were grouped into conjunctival lymphoma and "orbital-type" lymphoma (i.e., orbit, lacrimal gland, and lacrimal sac). Subjects were investigated for morphological changes in meibomian glands by meiboscore grading system. Radiation technique was examined and Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test, tear film break-up time (TBUT), slit lamp examination of corneal surface and lid margin abnormality were conducted before and after RT. RESULTS: The increase in meiboscore was statistically significant over time after RT in both groups (P < 0.001). The extent of increase in meiboscore was significantly greater in the "orbital-type" lymphoma group than in the conjunctival lymphoma group (P < 0.001). The changes in OSDI, TBUT, corneal fluorescein staining score and lid margin abnormality score after RT were significantly different across two groups (P = 0.042, 0.001, 0.035 and 0.001, respectively). Schirmer's value decreased after RT in both groups. Dry eye symptoms were most severe right after RT in both groups, but a gradual resolution was noted in most patients with conjunctival lymphoma, whereas symptoms persisted in "orbital-type" lymphoma patients. The OSDI score and corneal fluorescein staining score were positively correlated with meiboscore in "orbital-type" patients at post-RT 6 months (r = 0.43, P = 0.04; r = 0.39, P = 0.03, respectively). CONCLUSIONS: Patients with OAML had different degrees of morphological changes in meibomian glands according to tumor location and radiation technique. "Orbital-type" lymphoma patients are more likely to experience severe injury to meibomian glands, which eventually leads to persistent dry eye. Patients with "orbital-type" lymphoma should be well informed of post-RT damage on meibomian glands and persistent dry eye.


Assuntos
Síndromes do Olho Seco/etiologia , Neoplasias Oculares/radioterapia , Linfoma de Zona Marginal Tipo Células B/radioterapia , Glândulas Tarsais/efeitos da radiação , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Neoplasias da Túnica Conjuntiva/radioterapia , Síndromes do Olho Seco/diagnóstico , Feminino , Fluoresceína/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Humanos , Doenças do Aparelho Lacrimal/radioterapia , Masculino , Glândulas Tarsais/patologia , Pessoa de Meia-Idade , Neoplasias Orbitárias/radioterapia , Estudos Prospectivos , Lesões por Radiação/diagnóstico , Microscopia com Lâmpada de Fenda , Inquéritos e Questionários , Lágrimas/fisiologia , Adulto Jovem
17.
Int J Pharm ; 576: 119021, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31917298

RESUMO

The development of drug delivery vehicles to cancer and/or immune cells in lymph nodes is important for cancer diagnosis, therapy, and immunotherapy. We previously reported that anionic carboxyl-terminal dendrimers were accumulated in lymph nodes. In this study, three anionic dendrimers with carboxyl-, sulfonyl-, and phosphate-terminal groups were prepared to examine the lymph node targeting and the association with immune cells in the lymph nodes. These anionic dendrimers were accumulated in the lymph node by intradermal injection. Although the carboxyl- and sulfonyl-terminal dendrimers were diffused from the injection site, the phosphate-terminal dendrimers were mostly retained. The phosphate-terminal dendrimer was recognized by the macrophages, dendritic cells, and B cells in the lymph node, whereas the carboxyl- and sulfonyl-terminal dendrimers were not. Our results show that these anionic dendrimers were accumulated in the lymph node where the association with immune cells could be controlled by the terminal structure of the dendrimer. The phosphate-terminal dendrimer can be used as a nanoplatform for the delivery of some bioactive molecules to some immune cells, including B cells, in the lymph node.


Assuntos
Dendrímeros/farmacocinética , Portadores de Fármacos , Corantes Fluorescentes/farmacocinética , Linfonodos/metabolismo , Nanopartículas , Imagem Óptica , Animais , Dendrímeros/administração & dosagem , Dendrímeros/síntese química , Composição de Medicamentos , Feminino , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Injeções Intradérmicas , Linfonodos/diagnóstico por imagem , Linfonodos/imunologia , Camundongos Endogâmicos BALB C , Fosforilação , Distribuição Tecidual
18.
Mol Pharm ; 17(1): 109-117, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31816245

RESUMO

The endothelin (ET) axis plays a pivotal role in cardiovascular diseases. Enhanced levels of circulating ET-1 have been correlated with an inferior clinical outcome after myocardial infarction (MI) in humans. Thus, the evaluation of endothelin-A receptor (ETAR) expression over time in the course of myocardial injury and healing may offer valuable information toward the understanding of the ET axis involvement in MI. We developed an approach to track the expression of ETAR with a customized molecular imaging probe in a murine model of MI. The small molecular probe based on the ETAR-selective antagonist 3-(1,3-benzodioxol-5-yl)-5-hydroxy-5-(4-methoxyphenyl)-4-[(3,4,5-trimethoxyphenyl)methyl]-2(5H)-furanone (PD156707) was labeled with fluorescent dye, IRDye800cw. Mice undergoing permanent ligation of the left anterior descending artery (LAD) were investigated at day 1, 7, and 21 post surgery after receiving an intravenous injection of the ETAR probe. Cryosections of explanted hearts were analyzed by cryotome-based CCD, and fluorescence reflectance imaging (FRI) and fluorescence signal intensities (SI) were extracted. Fluorescence-mediated tomography (FMT) imaging was performed to visualize probe distribution in the target region in vivo. An enhanced fluorescence signal intensity in the infarct area was detected in cryoCCD images as early as day 1 after surgery and intensified up to 21 days post MI. FRI was capable of detecting significantly enhanced SI in infarcted regions of hearts 7 days after surgery. In vivo imaging by FMT localized enhanced SI in the apex region of infarcted mouse hearts. We verified the localization of the probe and ETAR within the infarct area by immunohistochemistry (IHC). In addition, neovascularized areas were found in the affected myocardium by CD31 staining. Our study demonstrates that the applied fluorescent probe is capable of delineating ETAR expression over time in affected murine myocardium after MI in vivo and ex vivo.


Assuntos
Dioxóis/metabolismo , Antagonistas dos Receptores de Endotelina/administração & dosagem , Corantes Fluorescentes/administração & dosagem , Infarto do Miocárdio/metabolismo , Receptores de Endotelina/metabolismo , Animais , Crioultramicrotomia , Dioxóis/química , Modelos Animais de Doenças , Antagonistas dos Receptores de Endotelina/análise , Antagonistas dos Receptores de Endotelina/química , Feminino , Corantes Fluorescentes/análise , Imuno-Histoquímica , Indóis/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/diagnóstico por imagem , Neovascularização Fisiológica , Imagem Óptica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo
19.
Talanta ; 208: 120279, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816747

RESUMO

Intracellular pH, especially cytoplasmic pH (~7.2) plays a crucial role in cell functions and metabolism. A ratiometric fluorescent probe namely, 6-(2-(benzothiazol-2-yl)vinyl)naphthalen-2-ol (BTNO) was facilely synthesized by the condensation of 6-hydroxy-2-naphthaldehyde and 2-methylbenzothiazole. BTNO exhibited a remarkable ratiometric emission (F456/F526) enhancement in response to a pH change with a linear range of pH = 9.50-7.00 and a pKa value of 7.91 ±â€¯0.03, which is desirable for measuring and monitoring the cytoplasmic pH fluctuations. In addition, because of the high fluorescence quantum yield of BTNO (Φ = 0.88 in DMSO and 0.61 in water relative to quinine sulfate solution in 0.1 M H2SO4), the interferences of the probe on the physiological functions could be greatly reduced. This could also provide enhanced measurement sensitivity. The successful demonstration of BTNO in detecting and monitoring the intracellular pH changes in live HeLa cells via a ratiometric approach confirmed that BTNO held a practical potential in biomedical research.


Assuntos
Citoplasma/metabolismo , Fluorescência , Corantes Fluorescentes/química , Imagem Molecular/métodos , Naftalenos/química , Triazóis/química , Proliferação de Células , Corantes Fluorescentes/administração & dosagem , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Naftalenos/administração & dosagem , Espectrometria de Fluorescência
20.
Int J Colorectal Dis ; 35(2): 269-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838580

RESUMO

PURPOSE: Some recent studies have suggested that fluorescence angiography with indocyanine green (ICG) might be useful for preventing anastomotic leakage (AL) after laparoscopic colorectal surgery. However, its efficacy has not been proven. We evaluated whether intraoperative ICG fluorescence angiography could decrease the AL rate with laparoscopic colorectal cancer surgery. METHODS: This retrospective study included patients with colorectal cancer who underwent laparoscopic surgery at our institution between March 2014 and December 2018. Patients were divided into two groups: with or without ICG fluorescence angiography. The primary outcome was the rate of AL. RESULTS: A total of 488 patients were included: 223 patients in the ICG group and 265 patients in the no-ICG group. In the ICG group, the transection line was changed to a more proximal location in seven patients (3.1%), including one patient with transverse colon surgery and six with rectal surgery. None of these seven patients developed AL. There were 18 ALs (3.7%) overall. The AL rate was 1.8% in the ICG group and 5.3% in the no-ICG group. For colon cancer, there were no significant differences in the AL rate between the groups (p = 0.278). In rectal cancer, the AL rate was significantly lower in the ICG group than in the no-ICG group (3.5% vs. 10.5%, p = 0.041). After propensity score matching, the AL rate was also significantly lower in the ICG group for rectal cancer (p = 0.044). CONCLUSION: ICG fluorescence angiography can potentially reduce the AL rate with laparoscopic rectal cancer surgery.


Assuntos
Fístula Anastomótica/prevenção & controle , Angiografia , Colectomia , Neoplasias Colorretais/cirurgia , Corantes Fluorescentes/administração & dosagem , Verde de Indocianina/administração & dosagem , Cuidados Intraoperatórios , Laparoscopia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fístula Anastomótica/etiologia , Colectomia/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
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