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A novel near-infrared fluorescence imaging probe that preferentially binds to cannabinoid receptors CB2R over CB1R.
Ling X, Zhang S, Shao P, Li W, Yang L, Ding Y, Xu C, Stella N, Bai M
(2015) Biomaterials 57: 169-78
MeSH Terms: Animals, Female, Fluorescent Dyes, Mice, Neoplasms, Optical Imaging, Receptors, Cannabinoid, Whole Body Imaging
Show Abstract · Added April 2, 2019
The type 2 cannabinoid receptors (CB2R) have gained much attention recently due to their important regulatory role in a host of pathophysiological processes. However, the exact biological function of CB2R and how this function might change depending on disease progression remains unclear and could be better studied with highly sensitive and selective imaging tools for identifying the receptors. Here we report the first near infrared fluorescence imaging probe (NIR760-XLP6) that binds preferentially to CB2R over the type 1 cannabinoid receptors (CB1R). The selectivity of the probe was demonstrated by fluorescence microscopy using DBT-CB2 and DBT-CB1 cells. Furthermore, in mouse tumor models, NIR760-XLP6 showed significantly higher uptake in DBT-CB2 than that in DBT-CB1 tumors. These findings indicate that NIR760-XLP6 is a promising imaging tool for the study of CB2R regulation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
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MeSH Terms
Toxicity studies of coumarin 6-encapsulated polystyrene nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide) as a colonoscopic imaging agent in rats.
Sakuma S, Kumagai H, Shimosato M, Kitamura T, Mohri K, Ikejima T, Hiwatari K, Koike S, Tobita E, McClure R, Gore JC, Pham W
(2015) Nanomedicine 11: 1227-36
MeSH Terms: Acetamides, Animals, Body Weight, CHO Cells, Caco-2 Cells, Colon, Colonoscopy, Colorectal Neoplasms, Coumarins, Cricetulus, Drinking, Eating, Fluorescent Dyes, Humans, Male, Nanospheres, Peanut Agglutinin, Polystyrenes, Polyvinyls, Rats, Rectum, Thiazoles
Show Abstract · Added February 15, 2016
UNLABELLED - We are investigating an imaging agent that detects early-stage primary colorectal cancer on the mucosal surface in real time under colonoscopic observation. The imaging agent, which is named the nanobeacon, is fluorescent nanospheres conjugated with peanut agglutinin and poly(N-vinylacetamide). Its potential use as an imaging tool for colorectal cancer has been thoroughly validated in numerous studies. Here, toxicities of the nanobeacon were assessed in rats. The nanobeacon was prepared according to the synthetic manner which is being established as the Good Manufacturing Practice-guided production. The rat study was performed in accordance with Good Laboratory Practice regulations. No nanobeacon treatment-related toxicity was observed. The no observable adverse effect levels (NOAEL) of the nanobeacon in 7-day consecutive oral administration and single intrarectal administration were estimated to be more than 1000mg/kg/day and 50mg/kg/day, respectively. We concluded that the nanobeacon could be developed as a safe diagnostic agent for colonoscopy applications.
FROM THE CLINICAL EDITOR - Colon cancer remains a major cause of death. Early detection can result in early treatment and thus survival. In this article, the authors tested potential systemic toxicity of coumarin 6-encapsulated polystyrene nanospheres conjugated with peanut agglutinin (PNA) and poly(N-vinylacetamide) (PNVA), which had been shown to bind specifically to colonic cancer cells and thus very promising in colonoscopic detection of cancer cells.
Copyright © 2015 Elsevier Inc. All rights reserved.
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2 Members
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22 MeSH Terms
Even free radicals should follow some rules: a guide to free radical research terminology and methodology.
Forman HJ, Augusto O, Brigelius-Flohe R, Dennery PA, Kalyanaraman B, Ischiropoulos H, Mann GE, Radi R, Roberts LJ, Vina J, Davies KJ
(2015) Free Radic Biol Med 78: 233-5
MeSH Terms: Animals, Antioxidants, Fluorescent Dyes, Free Radical Scavengers, Free Radicals, Humans, Lipid Peroxidation, Reactive Nitrogen Species, Reactive Oxygen Species, Terminology as Topic, Thiobarbituric Acid Reactive Substances
Show Abstract · Added February 15, 2016
Free radicals and oxidants are now implicated in physiological responses and in several diseases. Given the wide range of expertise of free radical researchers, application of the greater understanding of chemistry has not been uniformly applied to biological studies. We suggest that some widely used methodologies and terminologies hamper progress and need to be addressed. We make the case for abandonment and judicious use of several methods and terms and suggest practical and viable alternatives. These changes are suggested in four areas: use of fluorescent dyes to identify and quantify reactive species, methods for measurement of lipid peroxidation in complex biological systems, claims of antioxidants as radical scavengers, and use of the terms for reactive species.
Copyright © 2014 Elsevier Inc. All rights reserved.
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1 Members
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11 MeSH Terms
Fluorescent probes of the apoptolidins and their utility in cellular localization studies.
DeGuire SM, Earl DC, Du Y, Crews BA, Jacobs AT, Ustione A, Daniel C, Chong KM, Marnett LJ, Piston DW, Bachmann BO, Sulikowski GA
(2015) Angew Chem Int Ed Engl 54: 961-4
MeSH Terms: Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Fluorescent Dyes, Humans, Lipid Peroxidation, Macrolides, Microscopy, Confocal, Pyrones
Show Abstract · Added January 20, 2015
Apoptolidin A has been described among the top 0.1% most-cell-selective cytotoxic agents to be evaluated in the NCI 60 cell line panel. The molecular structure of apoptolidin A consists of a 20-membered macrolide with mono- and disaccharide moieties. In contrast to apoptolidin A, the aglycone (apoptolidinone) shows no cytotoxicity (>10 μM) when evaluated against several tumor cell lines. Apoptolidin H, the C27 deglycosylated analogue of apoptolidin A, displayed sub-micromolar activity against H292 lung carcinoma cells. Selective esterification of apoptolidins A and H with 5-azidopentanoic acid afforded azido-functionalized derivatives of potency equal to that of the parent macrolide. They also underwent strain-promoted alkyne-azido cycloaddition reactions to provide access to fluorescent and biotin-functionalized probes. Microscopy studies demonstrate apoptolidins A and H localize in the mitochondria of H292 human lung carcinoma cells.
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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4 Members
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9 MeSH Terms
Biocompatible mannosylated endosomal-escape nanoparticles enhance selective delivery of short nucleotide sequences to tumor associated macrophages.
Ortega RA, Barham WJ, Kumar B, Tikhomirov O, McFadden ID, Yull FE, Giorgio TD
(2015) Nanoscale 7: 500-10
MeSH Terms: Animals, Biocompatible Materials, Cell Line, Tumor, Cell Survival, Coculture Techniques, Drug Carriers, Endosomes, Female, Fluorescent Dyes, Lung, Lung Neoplasms, Macrophages, Mammary Neoplasms, Animal, Mannose, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Nanoparticles, Ovarian Neoplasms, Polymers, RNA, Small Interfering, Transplantation, Homologous, Tumor Microenvironment
Show Abstract · Added December 17, 2014
Tumor associated macrophages (TAMs) can modify the tumor microenvironment to create a pro-tumor niche. Manipulation of the TAM phenotype is a novel, potential therapeutic approach to engage anti-cancer immunity. siRNA is a molecular tool for knockdown of specific mRNAs that is tunable in both strength and duration. The use of siRNA to reprogram TAMs to adopt an immunogenic, anti-tumor phenotype is an attractive alternative to ablation of this cell population. One current difficulty with this approach is that TAMs are difficult to specifically target and transfect. We report here successful utilization of novel mannosylated polymer nanoparticles (MnNP) that are capable of escaping the endosomal compartment to deliver siRNA to TAMs in vitro and in vivo. Transfection with MnNP-siRNA complexes did not significantly decrease TAM cell membrane integrity in culture, nor did it create adverse kidney or liver function in mice, even at repeated doses of 5 mg kg(-1). Furthermore, MnNP effectively delivers labeled nucleotides to TAMs in mice with primary mammary tumors. We also confirmed TAM targeting in the solid tumors disseminated throughout the peritoneum of ovarian tumor bearing mice following injection of fluorescently labeled MnNP-nucleotide complexes into the peritoneum. Finally, we show enhanced uptake of MnNP in lung metastasis associated macrophages compared to untargeted particles when using an intubation delivery method. In summary, we have shown that MnNP specifically and effectively deliver siRNA to TAMs in vivo.
1 Communities
2 Members
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23 MeSH Terms
Molecular imaging of folate receptor β-positive macrophages during acute lung inflammation.
Han W, Zaynagetdinov R, Yull FE, Polosukhin VV, Gleaves LA, Tanjore H, Young LR, Peterson TE, Manning HC, Prince LS, Blackwell TS
(2015) Am J Respir Cell Mol Biol 53: 50-9
MeSH Terms: Acute Disease, Animals, Chemokine CCL2, Escherichia coli, Fluorescent Dyes, Folate Receptor 2, Gene Expression Regulation, Lipopolysaccharides, Macrophages, Alveolar, Mice, Mice, Knockout, Molecular Imaging, Pneumonia, Receptors, CCR2
Show Abstract · Added December 8, 2014
Characterization of markers that identify activated macrophages could advance understanding of inflammatory lung diseases and facilitate development of novel methodologies for monitoring disease activity. We investigated whether folate receptor β (FRβ) expression could be used to identify and quantify activated macrophages in the lungs during acute inflammation induced by Escherichia coli LPS. We found that FRβ expression was markedly increased in lung macrophages at 48 hours after intratracheal LPS. In vivo molecular imaging with a fluorescent probe (cyanine 5 polyethylene glycol folate) showed that the fluorescence signal over the chest peaked at 48 hours after intratracheal LPS and was markedly attenuated after depletion of macrophages. Using flow cytometry, we identified the cells responsible for uptake of cyanine 5-conjugated folate as FRβ(+) interstitial macrophages and pulmonary monocytes, which coexpressed markers associated with an M1 proinflammatory macrophage phenotype. These findings were confirmed using a second model of acute lung inflammation generated by inducible transgenic expression of an NF-κB activator in airway epithelium. Using CC chemokine receptor 2-deficient mice, we found that FRβ(+) macrophage/monocyte recruitment was dependent on the monocyte chemotactic protein-1/CC chemokine receptor 2 pathway. Together, our results demonstrate that folate-based molecular imaging can be used as a noninvasive approach to detect classically activated monocytes/macrophages recruited to the lungs during acute inflammation.
2 Communities
4 Members
0 Resources
14 MeSH Terms
Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve early detection of colorectal cancer.
Sakuma S, Yu JY, Quang T, Hiwatari K, Kumagai H, Kao S, Holt A, Erskind J, McClure R, Siuta M, Kitamura T, Tobita E, Koike S, Wilson K, Richards-Kortum R, Liu E, Washington K, Omary R, Gore JC, Pham W
(2015) Int J Cancer 136: 1095-103
MeSH Terms: Adenocarcinoma, Animals, Antigens, Tumor-Associated, Carbohydrate, Biomarkers, Tumor, Colonoscopy, Colorectal Neoplasms, Diagnostic Imaging, Early Detection of Cancer, Female, Fluorescence, Fluorescent Dyes, Immunoenzyme Techniques, Mice, Mice, Inbred C57BL, Nanospheres, Rats, Rats, Nude, Tumor Cells, Cultured
Show Abstract · Added February 12, 2015
Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.
© 2014 UICC.
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3 Members
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18 MeSH Terms
Molecular imaging of human tumor cells that naturally overexpress type 2 cannabinoid receptors using a quinolone-based near-infrared fluorescent probe.
Wu Z, Shao P, Zhang S, Ling X, Bai M
(2014) J Biomed Opt 19: 76016
MeSH Terms: Biomarkers, Tumor, Fluorescent Dyes, Humans, Jurkat Cells, Molecular Imaging, Molecular Probes, Quinolones, Receptor, Cannabinoid, CB2
Show Abstract · Added April 2, 2019
Cannabinoid CB2 receptors (CB2R) hold promise as therapeutic targets for treating diverse diseases, such as cancers, neurodegenerative diseases, pain, inflammation, osteoporosis, psychiatric disorders, addiction, and immune disorders. However, the fundamental role of CB2R in the regulation of diseases remains unclear, largely due to a lack of reliable imaging tools for the receptors. The goal of this study was to develop a CB2R-targeted molecular imaging probe and evaluate the specificity of the probe using human tumor cells that naturally overexpress CB2R. To synthesize the CB2R-targeted probe (NIR760-Q), a conjugable CB2R ligand based on the quinolone structure was first prepared, followed by bioconjugation with a near-infrared (NIR) fluorescent dye, NIR760. In vitro fluorescence imaging and competitive binding studies showed higher uptake of NIR760-Q than free NIR760 dye in Jurkat human acute T-lymphoblastic leukemia cells. In addition, the high uptake of NIR760-Q was significantly inhibited by the blocking agent, 4-quinolone-3-carboxamide, indicating specific binding of NIR760-Q to the target receptors. These results indicate that the NIR760-Q has potential in diagnostic imaging of CB2R positive cancers and elucidating the role of CB2R in the regulation of disease progression.
0 Communities
1 Members
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MeSH Terms
Specificity of lectin-immobilized fluorescent nanospheres for colorectal tumors in a mouse model which better resembles the clinical disease.
Kitamura T, Sakuma S, Shimosato M, Higashino H, Masaoka Y, Kataoka M, Yamashita S, Hiwatari K, Kumagai H, Morimoto N, Koike S, Tobita E, Hoffman RM, Gore JC, Pham W
(2015) Contrast Media Mol Imaging 10: 135-43
MeSH Terms: Animals, Cell Line, Tumor, Colorectal Neoplasms, Female, Fluorescent Dyes, Humans, Intestinal Mucosa, Lectins, Mice, Mice, Nude, Nanospheres, Neoplasms, Experimental, Optical Imaging
Show Abstract · Added February 12, 2015
We have been investigating an imaging agent that enables real-time and accurate diagnosis of early colorectal cancer at the intestinal mucosa by colonoscopy. The imaging agent is peanut agglutinin-immobilized polystyrene nanospheres with surface poly(N-vinylacetamide) chains encapsulating coumarin 6. Intracolonically-administered lectin-immobilized fluorescent nanospheres detect tumor-derived changes through molecular recognition of lectin for the terminal sugar of cancer-specific antigens on the mucosal surface. The focus of the present study was to evaluate imaging abilities of the nanospheres in animal models that reflect clinical environments. We previously developed an orthotopic mouse model with human colorectal tumors growing on the mucosa of the descending colon to better resemble the clinical disease. The entire colon of the mice in the exposed abdomen was monitored in real time with an in vivo imaging apparatus. Fluorescence from the nanospheres was observed along the entire descending colon after intracolonical administration from the anus. When the luminal side of the colon was washed with phosphate-buffered saline, most of the nanospheres were flushed. However, fluorescence persisted in areas where cancer cells were implanted. Histological evaluation demonstrated that tumors were present in the mucosal epithelia where the nanospheres fluoresced. In contrast, no fluorescence was observed when control mice, without tumors were tested. The lectin-immobilized fluorescent nanospheres were tumor-specific and remained bound to tumors even after vigorous washing. The nanospheres nonspecifically bound to normal mucosa were easily removed through mild washing. These results indicate that the nanospheres combined with colonoscopy, will be a clinically-valuable diagnostic tool for early-stage primary colon carcinoma.
Copyright © 2014 John Wiley & Sons, Ltd.
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1 Members
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13 MeSH Terms
Perfluorocarbon nanoemulsions with fluorescent, colloidal and magnetic properties.
Janjic JM, Shao P, Zhang S, Yang X, Patel SK, Bai M
(2014) Biomaterials 35: 4958-68
MeSH Terms: Animals, Cell Line, Tumor, Cell Survival, Emulsions, Fluorescent Dyes, Fluorocarbons, Magnetic Resonance Imaging, Mice, Nanostructures, Particle Size, Spectroscopy, Near-Infrared, Surface-Active Agents
Show Abstract · Added April 2, 2019
Bimodal imaging agents that combine magnetic resonance imaging (MRI) and nearinfrared (NIR) imaging formulated as nanoemulsions became increasingly popular for imaging inflammation in vivo. Quality of in vivo imaging using nanoemulsions is directly dependent on their integrity and stability. Here we report the design of nanoemulsions for bimodal imaging, where both photostability and colloidal stability are equally addressed. A highly chemically and photo stable quaterrylenediimide dye was introduced into perfluoro-15-crown-5 ether (PCE) nanoemulsions. The nanoemulsions were prepared with PCE and Miglyol 812N mixed at 1:1 v/v ratio as internal phase stabilized by non-ionic surfactants. Data shows exceptional colloidal stability demonstrated as unchanged droplet size (~130 nm) and polydispersity (<0.15) after 182 days follow up at both 4 and 25 °C. Nanoemulsions also sustained the exposure to mechanical and temperature stress, and prolonged exposure to light without changes in droplet size, (19)F signal or fluorescence signal. No toxicity was observed in vitro in model inflammatory cells upon 24 h exposure while confocal microscopy showed that nanoemulsions droplets accumulated in the cytoplasm. Overall, our data demonstrates that design of bimodal imaging agents requires consideration of stability of each imaging component and that of the nanosystem as a whole to achieve excellent imaging performance.
Copyright © 2014 Elsevier Ltd. All rights reserved.
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1 Members
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MeSH Terms