Modulating cellular cytotoxicity and phototoxicity of fluorescent organic salts through counterion pairing

Abstract Light-activated theranostics offer promising opportunities for disease diagnosis, image-guided surgery, and site-specific personalized therapy. However, current fluorescent dyes are limited by low brightness, high cytotoxicity, poor tissue penetration, and unwanted side effects. To overcome these limitations, we demonstrate a platform for optoelectronic tuning, which allows independent control of the optical properties from the electronic properties of fluorescent organic salts. This is achieved through cation-anion pairing of organic salts that can modulate the frontier molecular orbital without impacting the bandgap. Optoelectronic tuning enables decoupled control over the cytotoxicity and phototoxicity of fluorescent organic salts by selective generation of mitochondrial reactive oxygen species that control cell viability. We show that through counterion pairing, organic salt nanoparticles can be tuned to be either nontoxic for enhanced imaging, or phototoxic for improved photodynamic therapy.

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Modulating cellular cytotoxicity and phototoxicity of fluorescent organic salts through counterion pairing

10.1101/743716 ◽

2019 ◽

Author(s):

Deanna Broadwater ◽

Matthew Bates ◽

Mayank Jayaram ◽

Margaret Young ◽

Jianzhou He ◽

...

Keyword(s):

Fluorescent Dyes ◽

Control Cell ◽

Disease Diagnosis ◽

Frontier Molecular Orbital ◽

Organic Salt ◽

Organic Salts ◽

Guided Surgery ◽

Decoupled Control ◽

Selective Generation ◽

High Cytotoxicity

Light-activated theranostics offer promising opportunities for disease diagnosis, image-guided surgery, and site-specific personalized therapy. However, current fluorescent dyes are limited by low brightness, high cytotoxicity, poor tissue penetration, and unwanted side effects. To overcome these limitations, we demonstrate a platform for optoelectronic tuning, which allows independent control of the optical properties from the electronic properties of fluorescent organic salts. This is achieved through cation-anion pairing of organic salts that can modulate the frontier molecular orbital without impacting the bandgap. Optoelectronic tuning enables decoupled control over the cytotoxicity and phototoxicity of fluorescent organic salts through selective generation of mitochondrial reactive oxygen species that control cell viability. We show that through counterion pairing, organic salt nanoparticles can be tuned to be either nontoxic for enhanced imaging, or phototoxic for improved photodynamic therapy.

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Hyperspectral Imaging for Clinical Applications

BioChip Journal ◽

10.1007/s13206-021-00041-0 ◽

2022 ◽

Author(s):

Jonghee Yoon

Keyword(s):

Hyperspectral Imaging ◽

Fluorescent Dyes ◽

Disease Diagnosis ◽

Clinical Applications ◽

Optical Systems ◽

Clinical Implementation ◽

Significant Information ◽

Surgical Guidance ◽

Guided Surgery ◽

Clinically Significant

AbstractMeasuring morphological and biochemical features of tissue is crucial for disease diagnosis and surgical guidance, providing clinically significant information related to pathophysiology. Hyperspectral imaging (HSI) techniques obtain both spatial and spectral features of tissue without labeling molecules such as fluorescent dyes, which provides rich information for improved disease diagnosis and treatment. Recent advances in HSI systems have demonstrated its potential for clinical applications, especially in disease diagnosis and image-guided surgery. This review summarizes the basic principle of HSI and optical systems, deep-learning-based image analysis, and clinical applications of HSI to provide insight into this rapidly growing field of research. In addition, the challenges facing the clinical implementation of HSI techniques are discussed.

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Optical imaging probes and their potential contribution to radiotracer development

Nuklearmedizin ◽

10.1055/s-0037-1616473 ◽

2016 ◽

Vol 55 (02) ◽

pp. 51-62 ◽

Cited By ~ 3

Author(s):

S. Hermann ◽

M. Schäfers ◽

C. Höltke ◽

A. Faust

Keyword(s):

Optical Imaging ◽

Fluorescent Dyes ◽

Great Influence ◽

Potential Contribution ◽

Preclinical Evaluation ◽

Guided Surgery ◽

Fluorescence Guided Surgery ◽

Imaging Probes ◽

Unspecific Binding

SummaryOptical imaging has long been considered a method for histological or microscopic investigations. Over the last 15 years, however, this method was applied for preclinical molecular imaging and, just recently, was also able to show its principal potential for clinical applications (e.g. fluorescence-guided surgery). Reviewing the development and preclinical evaluation of new fluorescent dyes and target-specific dye conjugates, these often show characteristic patterns of their routes of excretion and biodistribution, which could also be interesting for the development and optimization of radiopharmaceuticals. Especially ionic charges show a great influence on biodistribution and netcharge and charge-distribution on a conjugate often determines unspecific binding or background signals in liver, kidney or intestine, and other organs.Learning from fluorescent probe behaviour in vivo and translating this knowledge to radio-pharmaceuticals might be useful to further optimize emerging and existing radiopharmaceuticals with respect to their biodistribution and thereby availability for binding to their targets.

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Recent Advances in Quenchbody, a Fluorescent Immunosensor

Sensors ◽

10.3390/s21041223 ◽

2021 ◽

Vol 21 (4) ◽

pp. 1223

Author(s):

Jinhua Dong ◽

Hiroshi Ueda

Keyword(s):

Fluorescence Intensity ◽

Fluorescent Dyes ◽

Antibody Fragment ◽

Disease Diagnosis ◽

Disease Biomarkers ◽

Highly Sensitive ◽

Physiologically Active Substances ◽

New Type ◽

Antigen Antibody ◽

Active Substances

The detection of viruses, disease biomarkers, physiologically active substances, drugs, and chemicals is of great significance in many areas of our lives. Immunodetection technology is based on the specificity and affinity of antigen–antibody reactions. Compared with other analytical methods such as liquid chromatography coupled with mass spectrometry, which requires a large and expensive instrument, immunodetection has the advantages of simplicity and good selectivity and is thus widely used in disease diagnosis and food/environmental monitoring. Quenchbody (Q-body), a new type of fluorescent immunosensor, is an antibody fragment labeled with fluorescent dyes. When the Q-body binds to its antigen, the fluorescence intensity increases. The detection of antigens by changes in fluorescence intensity is simple, easy to operate, and highly sensitive. This review comprehensively discusses the principle, construction, application, and current progress related to Q-bodies.

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The potential contribution of organic salts to new particle growth

Atmospheric Chemistry and Physics ◽

10.5194/acp-9-2949-2009 ◽

2009 ◽

Vol 9 (9) ◽

pp. 2949-2957 ◽

Cited By ~ 134

Author(s):

K. C. Barsanti ◽

P. H. McMurry ◽

J. N. Smith

Keyword(s):

Organic Acids ◽

Particle Growth ◽

Estimation Methods ◽

Organic Salt ◽

Pure Liquid ◽

Potential Contribution ◽

Salt Formation ◽

Organic Salts ◽

Acids And Bases ◽

Atmospherically Relevant

Abstract. Field and lab measurements suggest that low-molecular weight (MW) organic acids and bases exist in accumulation and nucleation mode particles, despite their relatively high pure-liquid vapor pressures. The mechanism(s) by which such compounds contribute to the mass growth of existing aerosol particles and newly formed particles has not been thoroughly explored. One mechanism by which low-MW compounds may contribute to new particle growth is through the formation of organic salts. In this paper we use thermodynamic modeling to explore the potential for organic salt formation by atmospherically relevant organic acids and bases for two system types: one in which the relative contribution of ammonia vs. amines in forming organic salts was evaluated, the other in which the decrease in volatility of organic acids and bases due to organic salt formation was assessed. The modeling approach employed relied heavily on group contribution and other estimation methods for necessary physical and chemical parameters. The results of this work suggest that amines may be an important contributor to organic salt formation, and that experimental data are greatly needed to improve our understanding of organic salt formation in atmospherically relevant systems and to accurately predict the potential contribution of such salts to new particle growth.

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Inorganic salts interact with organic di-acids in sub-micron particles to form material with low hygroscopicity and volatility

Atmospheric Chemistry and Physics Discussions ◽

10.5194/acpd-13-30653-2013 ◽

2013 ◽

Vol 13 (11) ◽

pp. 30653-30685

Author(s):

G. Drozd ◽

J. Woo ◽

S. A. K. Häkkinen ◽

A. Nenes ◽

V. F. McNeill

Keyword(s):

Current Knowledge ◽

Inorganic Ions ◽

Organic Salt ◽

Formation Mechanisms ◽

Organic Salts ◽

Low Viscosity ◽

Organic Complexes ◽

Mass Fractions ◽

Hygroscopic Salts ◽

Divalent Salts

Abstract. Volatility and hygroscopicity are two key properties of organic aerosol components, and both are strongly related to chemical identity. Here we show that inorganic-organic component interactions typically not considered in atmospheric models may strongly affect aerosol volatility and hygroscopicity. In particular, bi-dentate binding of di-carboxylic acids (DCA) to soluble inorganic ions can lead to very strongly bound metal-organic complexes with largely undetermined hygroscopicity and volatility. These reactions profoundly impact particle hygroscopicity, transforming hygroscopic components into irreversibly non-hygroscopic material. While the hygroscopicities of pure salts, DCA, and DCA salts are known, the hygroscopicity of internal mixtures of hygroscopic salts and DCA, as they are typically found in the atmosphere, has not been fully characterized. We have studied the volatility of pure, dry organic salt particles and the hygroscopicity of internal mixtures of oxalic acid (OxA, the dominant DCA in the atmosphere) and a number of salts, both mono- and di-valent. The formation of very low volatility organic salts was confirmed, with minimal evaporation of oxalate salt particles below 75 °C. Dramatic increases in the CCN activation diameter for particles with divalent salts (e.g. CaCl2) and relatively small particle mass fractions of OxA indicate that standard volume additivity rules for hygroscopicity do not apply. Thus small organic compounds with high O:C are capable of forming low volatility and very low hygroscopicity particles. Given current knowledge of the formation mechanisms of OxA and M-Ox salts, surface enrichment of insoluble M-Ox salts is expected. The resulting formation of an insoluble coating of metal-oxalate salts can explain low particle hygroscopicities. The formation of particles with a hard coating could offer an alternative explanation for observations of glass-like particles with very low viscosity.

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Synthesis of N-Tetradecyl-1,10-phenathrolinium-Based New Salts for Biological Applications

Bioinorganic Chemistry and Applications ◽

10.1155/2018/8097483 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Atakilt Abebe ◽

Minaleshewa Atlabachew ◽

Misganaw Liyew ◽

Elsabet Ferede

Keyword(s):

Photoelectron Spectroscopy ◽

Biological Activities ◽

Thermal Characterization ◽

Organic Salt ◽

Ionization Mass ◽

Gram Negative Bacteria ◽

Organic Salts ◽

Gram Negative ◽

Ionization Mass Spectroscopy ◽

Tga And Dsc

New organic salts were synthesized by quaternizing 1,10-phenanthroline using 1-bromotetradecane. The first step yielded an organic salt of formula [C26H37N2]Br. Anion exchange reaction using Li[(CF3SO2)2N] resulted in a more stable salt of formula [C26H37N2][(CF3SO2)2N]. The organic salts were investigated by spectrometry (1H, 13C, 19F NMR, X-ray photoelectron spectroscopy (XPS), UV-Vis, and matrix-assisted laser desorption/ionization mass spectroscopy (MALDI MS), CHNSBr elemental analysis, and thermal analysis (TGA and DSC). The thermal characterization showed the melting and decomposition points of [C26H37N2][(CF3SO2)2N] to be 48°C and 290°C, respectively, which indicates it is an ionic liquid with large liquidus range. The biological activities of the salts were investigated against two Gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and two Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria, and they are found to be active against all of them. They were compared with [Cu(1,10-phenanthroline)2Cl]Cl. They are found more active against the Gram-negative bacteria. The salts demonstrated minimum inhibitory concentration as low as 50 µg/L. These results suggest the synthesized salts can be considered as a better alternative to certain transition metal complex drugs. This minimizes the concern of introducing metal ions into the organism.

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Effects and Mechanism of Organic Acids on Aluminum Availability of Dark Brown Forest Soil

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.393-395.709 ◽

2011 ◽

Vol 393-395 ◽

pp. 709-712 ◽

Cited By ~ 1

Author(s):

Fu Xing Cui ◽

Jin Feng Song ◽

Ya Fen Guo ◽

Jin Zhong Xu

Keyword(s):

Citric Acid ◽

Oxalic Acid ◽

Organic Acids ◽

Organic Acid ◽

Forest Soil ◽

Dissociation Constants ◽

Organic Salt ◽

Brown Forest Soil ◽

Organic Salts ◽

Complexation Reactions

The effects and mechanism of different concentration organic acids and organic salts solution on Al availability of dark brown forest soil were studied. It was resulted that, oxalic acid/oxalate and citric acid/citrate substantially stimulated soil Al release of dark brown forest soil. The effect of organic acids/salts on Al release would be strengthen with increasing of their concentrations.The contents of Al released from A1 horizon was higher than that from B horizon. Organic salt solutions had much higher effects than organic acid the same in concentration, i.e. citrate>citric acid, oxalate>oxalic acid. Therefore, the mechanism of organic acid/salts triggering release of soil Al was assumed to be dominated by complexation reactions of organic anions. Citric acid/ citrate had much higher effect than oxalic acid/ oxalate at same concentration to A1 and B horizons, i.e. citrate> oxalate, citric acid>oxalic acid, which was primarily related with the greater complexing capacities and dissociation constants of citric acid.

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Six-armed Structures Based on Benzene Ring, Synthesis and Characterization Via Sonogashira Coupling

Indonesian Journal of Chemistry ◽

10.22146/ijc.49419 ◽

2020 ◽

Vol 20 (3) ◽

pp. 705

Author(s):

Mohammed Hadi Ali Al-Jumaili ◽

Ahmed Solaiman Hamed ◽

Nihat Akkurt ◽

Lokman Torun

Keyword(s):

Differential Scanning Calorimetry ◽

Benzene Ring ◽

Organic Salt ◽

Synthesis And Characterization ◽

Spectroscopic Methods ◽

Sonogashira Coupling ◽

Scanning Calorimetry ◽

Organic Salts ◽

Crystal Property ◽

Liquid Crystal Property

A new six-armed compounds consist of benzene ring as a central core substituted with aromatic ring and three rod-like armed of 2-chloro-4,6-bis(dodecyloxy)-1,3,5-triazine as the peripheral arms unit which obtained by sequential nucleophilic substitution of chlorine atoms in cyanuric chloride. The substitution took place at the acetylenic periphery on the central benzene ring by Sonogashira coupling. Equimolar mixtures of the six-armed compounds based on the benzene core with the complementary 4-dodecyloxybenzoic acid, which already possessed liquid crystal property, resulted in an organic salt. The organic salts and structures were investigated by differential scanning calorimetry (DSC), and confirmed by spectroscopic methods (1H-NMR, 13C-NMR and Mass spectroscopy)

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A Deep Learning Framework for Segmenting Brain Tumors Using MRI and Synthetically Generated CT Images

Sensors ◽

10.3390/s22020523 ◽

2022 ◽

Vol 22 (2) ◽

pp. 523

Author(s):

Kh Tohidul Islam ◽

Sudanthi Wijewickrema ◽

Stephen O’Leary

Keyword(s):

Image Segmentation ◽

Three Dimensional ◽

Disease Diagnosis ◽

Ct Images ◽

Medical Image Segmentation ◽

Tumor Segmentation ◽

Brain Tumor Segmentation ◽

Learning Framework ◽

Guided Surgery ◽

Magnetic Resonance Imaging Mri

Multi-modal three-dimensional (3-D) image segmentation is used in many medical applications, such as disease diagnosis, treatment planning, and image-guided surgery. Although multi-modal images provide information that no single image modality alone can provide, integrating such information to be used in segmentation is a challenging task. Numerous methods have been introduced to solve the problem of multi-modal medical image segmentation in recent years. In this paper, we propose a solution for the task of brain tumor segmentation. To this end, we first introduce a method of enhancing an existing magnetic resonance imaging (MRI) dataset by generating synthetic computed tomography (CT) images. Then, we discuss a process of systematic optimization of a convolutional neural network (CNN) architecture that uses this enhanced dataset, in order to customize it for our task. Using publicly available datasets, we show that the proposed method outperforms similar existing methods.

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