scholarly journals Revealing the Distribution of Aggregation-Induced Emission Nanoparticles via Dual-Modality Imaging with Fluorescence and Mass Spectrometry

Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Liucheng Mao ◽  
Yuming Jiang ◽  
Hui Ouyang ◽  
Yulin Feng ◽  
Ruoxin Li ◽  
...  

Aggregation-induced emission nanoparticles (AIE NPs) are widely used in the biomedical field. However, understanding the biological process of AIE NPs via fluorescence imaging is challenging because of the strong background and poor penetration depth. Herein, we present a novel dual-modality imaging strategy that combines fluorescence imaging and label-free laser desorption/ionization mass spectrometry imaging (LDI MSI) to map and quantify the biodistribution of AIE NPs (TPAFN-F127 NPs) by monitoring the intrinsic photoluminescence and mass spectrometry signal of the AIE molecule. We discovered that TPAFN-F127 NPs were predominantly distributed in the liver and spleen, and most gradually excreted from the body after 5 days. The accumulation and retention of TPAFN-F127 NPs in tumor sites were also confirmed in a tumor-bearing mouse model. As a proof of concept, the suborgan distribution of TPAFN-F127 NPs in the spleen was visualized by LDI MSI, and the results revealed that TPAFN-F127 NPs were mainly distributed in the red pulp of the spleen with extremely high concentrations within the marginal zone. The in vivo toxicity test demonstrated that TPAFN-F127 NPs are nontoxic for a long-term exposure. This dual-modality imaging strategy provides some insights into the fine distribution of AIE NPs and might also be extended to other polymeric NPs to evaluate their distribution and drug release behaviors in vivo.

2018 ◽  
Vol 4 (10) ◽  
pp. eaat9039 ◽  
Author(s):  
Jinjuan Xue ◽  
Huihui Liu ◽  
Suming Chen ◽  
Caiqiao Xiong ◽  
Lingpeng Zhan ◽  
...  

It is crucial but of a great challenge to study in vivo and in situ drug release of nanocarriers when developing a nanomaterial-based drug delivery platform. We developed a new label-free laser desorption/ionization mass spectrometry (MS) imaging strategy that enabled visualization and quantification of the in situ drug release in tissues by monitoring intrinsic MS signal intensity ratio of loaded drug over the nanocarriers. The proof of concept was demonstrated by investigating the doxorubicin (DOX)/polyethylene glycol–MoS2 nanosheets drug delivery system in tumor mouse models. The results revealed a tissue-dependent release behavior of DOX during circulation with the highest dissociation in tumor and lowest dissociation in liver tissues. The drug-loaded MoS2 nanocarriers are predominantly distributed in lung, spleen, and liver tissues, whereas the accumulation in the tumor was unexpectedly lower than in normal tissues. This new strategy could also be extended to other drug-carrier systems, such as carbon nanotubes and black phosphorus nanosheets, and opened a new path to evaluate the drug release of nanocarriers in the suborgan level.


2021 ◽  
pp. 247255522110006
Author(s):  
Michael D. Scholle ◽  
Zachary A. Gurard-Levin

Arginase-1, an enzyme that catalyzes the reaction of L-arginine to L-ornithine, is implicated in the tumor immune response and represents an interesting therapeutic target in immuno-oncology. Initiating arginase drug discovery efforts remains a challenge due to a lack of suitable high-throughput assay methodologies. This report describes the combination of self-assembled monolayers and matrix-assisted laser desorption ionization mass spectrometry to enable the first label-free and high-throughput assay for arginase activity. The assay was optimized for kinetically balanced conditions and miniaturized, while achieving a robust assay (Z-factor > 0.8) and a significant assay window [signal-to-background ratio > 20] relative to fluorescent approaches. To validate the assay, the inhibition of the reference compound nor-NOHA (Nω-hydroxy-nor-L-arginine) was evaluated, and the IC50 measured to be in line with reported results (IC50 = 180 nM). The assay was then used to complete a screen of 175,000 compounds, demonstrating the high-throughput capacity of the approach. The label-free format also eliminates opportunities for false-positive results due to interference from library compounds and optical readouts. The assay methodology described here enables new opportunities for drug discovery for arginase and, due to the assay flexibility, can be more broadly applicable for measuring other amino acid–metabolizing enzymes.


2015 ◽  
Vol 2 (Suppl 1) ◽  
pp. A89 ◽  
Author(s):  
Charalmpos Tsoukalas ◽  
Gautier Laurent ◽  
Gloria Jiménez Sánchez ◽  
Theodoros Tsotakos ◽  
Rana Bazzi ◽  
...  

2017 ◽  
Vol 22 (10) ◽  
pp. 1246-1252 ◽  
Author(s):  
Kishore Kumar Jagadeesan ◽  
Simon Ekström

Recently, mass spectrometry (MS) has emerged as an important tool for high-throughput screening (HTS) providing a direct and label-free detection method, complementing traditional fluorescent and colorimetric methodologies. Among the various MS techniques used for HTS, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides many of the characteristics required for high-throughput analyses, such as low cost, speed, and automation. However, visualization and analysis of the large datasets generated by HTS MALDI-MS can pose significant challenges, especially for multiparametric experiments. The datasets can be generated fast, and the complexity of the experimental data (e.g., screening many different sorbent phases, the sorbent mass, and the load, wash, and elution conditions) makes manual data analysis difficult. To address these challenges, a comprehensive informatics tool called MALDIViz was developed. This tool is an R-Shiny-based web application, accessible independently of the operating system and without the need to install any program locally. It has been designed to facilitate easy analysis and visualization of MALDI-MS datasets, comparison of multiplex experiments, and export of the analysis results to high-quality images.


2021 ◽  
Vol 11 (22) ◽  
pp. 11038
Author(s):  
Yudai Tsuji ◽  
Shinichi Yamaguchi ◽  
Tomoyuki Nakamura ◽  
Masaya Ikegawa

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is increasingly used in a broad range of research due to its ability to visualize the spatial distribution of metabolites in vivo. Here, we have developed a method, named thoracic Mass Spectrometry Imaging (tMSI), as a standard protocol of molecular imaging of whole-animal sectioning in various settings of mice in vivo. Further application of the strategy that involved the systemic administration of dexamethasone (DEX) in mice, enabled a dynamic shift in the energy status of multiple thoracic organs to be visualized, based on tMSI data of purine and pyrimidine metabolites. Furthermore, with the introduction of uniform manifold approximation and projection (UMAP) for tMSI data, metabolic profiles normally localized in the cortex and cortico-medullary junction (CMJ) of the thymus were drastically shifted as minor profiles into the medulla of DEX-treated thymus. As a massive apoptotic cell death in the thymic cortex was noticeable, a single molecule, which was upregulated in the cortex of the thymus, enabled us to predict ongoing immunosuppression by in vivo DEX-administration.


2016 ◽  
Vol 88 (1) ◽  
pp. 281-292 ◽  
Author(s):  
CHARLENE S.C. GARCIA ◽  
CAROLINE MENTI ◽  
ANA PAULA F. LAMBERT ◽  
THIAGO BARCELLOS ◽  
SIDNEI MOURA ◽  
...  

ABSTRACT Salvia officinalis (Lamiaceae) has been used in south of Brazil as a diary homemade, in food condiment and tea-beverage used for the treatment of several disorders. The objective of this study was to characterize chemical compounds in the hydroalcoholic (ExtHS) and aqueous (ExtAS) extract from Salvia officinalis (L.) by gas chromatography-mass spectrometry (GC-MS) and by high-resolution electrospray ionization mass spectrometry (ESI-QTOF MS/MS), evaluate in vitro ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•+), catalase (CAT-like) and superoxide dismutase (SOD-like) activity, moreover cytotoxic by MTT assay, alterations on cell morphology by giemsa and apoptotic-induced mechanism for annexin V/propidium iodide. Chemical identification sage extracts revealed the presence of acids and phenolic compounds. In vitro antioxidant analysis for both extracts indicated promising activities. The cytotoxic assays using tumor (Hep-2, HeLa, A-549, HT-29 and A-375) and in non-tumor (HEK-293 and MRC-5), showed selectivity for tumor cell lines. Immunocytochemistry presenting a majority of tumor cells at late stages of the apoptotic process and necrosis. Given the results presented here, Brazilian Salvia officinalis (L.) used as condiment and tea, may protect the body against some disease, in particularly those where oxidative stress is involved, like neurodegenerative disorders, inflammation and cancer.


2012 ◽  
Vol 163 (2) ◽  
pp. 249-255 ◽  
Author(s):  
Jaehong Key ◽  
Christy Cooper ◽  
Ah Young Kim ◽  
Deepika Dhawan ◽  
Deborah W. Knapp ◽  
...  

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