Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Chemical Reviews, Год журнала: 2017, Номер 117(15), С. 10043 - 10120

Опубликована: Июнь 27, 2017

Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, effective way to deliver drugs specifically mitochondria is by covalent linking a lipophilic cation such an alkyltriphenylphosphonium moiety pharmacophore interest. Other delocalized cations, rhodamine, natural synthetic mitochondria-targeting peptides, nanoparticle vehicles, have also been used mitochondrial delivery small molecules. Depending on approach used, cell membrane potentials, more than 1000-fold higher concentration can be achieved. Mitochondrial targeting has developed study physiology dysfunction interaction between other subcellular organelles treatment variety diseases neurodegeneration cancer. In this Review, we discuss efforts target small-molecule compounds probing function, diagnostic tools potential therapeutics. We describe physicochemical basis accumulation chemistry strategies mitochondria, probes, sensors, examples bioactive compounds. Finally, review published attempts apply mitochondria-targeted agents cancer neurodegenerative

Язык: Английский

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Fluorescent probes for organelle-targeted bioactive species imaging

Chemical Science, Год журнала: 2019, Номер 10(24), С. 6035 - 6071

Опубликована: Янв. 1, 2019

The dynamic fluctuations of bioactive species in living cells are associated with numerous physiological and pathological phenomena. emergence organelle-targeted fluorescent probes has significantly facilitated our understanding on the biological functions these species. This review describes design, applications, challenges potential directions probes.

Язык: Английский

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Selective Visualization of the Endogenous Peroxynitrite in an Inflamed Mouse Model by a Mitochondria-Targetable Two-Photon Ratiometric Fluorescent Probe

Journal of the American Chemical Society, Год журнала: 2016, Номер 139(1), С. 285 - 292

Опубликована: Дек. 5, 2016

Peroxynitrite (ONOO–) is a kind of reactive oxygen species (ROS) with super activity oxidization and nitration, overproduction ONOO– associated pathogenesis many diseases. Thus, accurate detection high sensitivity selectivity imperative for elucidating its functions in health or disease states. Herein we the first time present new two-photon ratiometric fluorescent probe (MITO-CC) based on FRET mechanism by combining rational design strategy dye-screening approach. MITO-CC, fast response rate (within 20 s), excellent (detection limit = 11.30 nM) outstanding toward ONOO–, was successfully applied to endogenous produced HepG2/RAW264.7 cells further employed imaging oxidative stress an inflamed mouse model. Therefore, MITO-CC could be potential biological tool explore roles under different physiological pathological settings.

Язык: Английский

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A General Method To Increase Stokes Shift by Introducing Alternating Vibronic Structures

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(24), С. 7716 - 7722

Опубликована: Май 24, 2018

Fluorescent dyes have enabled much progress in the broad range of biomedical fields. However, many commercially available suffer from small Stokes shifts, resulting poor signal-to-noise ratio and self-quenching on current microscope configurations. In this work, we developed a general method to significantly increase shifts common fluorophores. By simply appending 1,4-diethyl-decahydro-quinoxaline (DQ) moiety onto conjugated structure, introduced vibronic backbone that could facilely expand emission wavelength, photostability 11 different fluorophores by more than 3-fold. This generalizable improve imaging efficiency commercial As demonstration, showed DQ derivative hemicyanine generated 5-fold signal mouse models over indocyanine green. Furthermore, DQ-modified pair with their parent molecules conduct one-excitation, multiple imaging, allowing us study cell behavior robustly. approach shows promise generating suitable for super-resolution microscopy second window near-infrared imaging.

Язык: Английский

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Cellular Uptake of Nanoparticles versus Small Molecules: A Matter of Size

Accounts of Chemical Research, Год журнала: 2018, Номер 51(9), С. 2305 - 2313

Опубликована: Авг. 29, 2018

ConspectusThe primary function of the cell membrane is to protect cells from their surroundings. This entails a strict regulation on controlling exchange matter between and its environment. A key factor when considering potential biological applications particular chemical structure has do with ability internalize into cells. Molecules that can readily cross membranes are frequently needed in research medicine, since most therapeutic entities designed modulate intracellular components. However, design molecules not penetrate also relevant toward, for example, extracellular contrast agents, which widely used clinical diagnosis.Small have occupied forefront biomedical until recently, but past few decades seen an increasing use larger structures, such as proteins or nanoparticles, leading unprecedented often unexpectedly novel research. Great achievements been made toward understanding rules govern cellular uptake, show internalization largely affected by size. For macromolecules nucleic acids usually unable Intriguingly, case sizes seem facilitate via endocytic pathways, through particles remain trapped lysosomes endosomes.In this Account, we aimed at presenting our personal view how different structures behave terms due size, ranging small drugs large nanoparticles. We first introduce properties main mechanisms involved uptake. then discuss molecules, distinguishing those molecular weights below 1 kDa acids. In last section, review behavior special emphasis plasmonic feature high field. each group parameters affecting strategies be applied achieve desired delivery. Particular attention paid approaches allow conditional process using external triggers, activable penetrating peptides, impact these systems may drug delivery sensing applications. The Account ends "Conclusions Outlook" where general lessons future directions further advancements briefly presented.

Язык: Английский

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Fluorescent nucleobases as tools for studying DNA and RNA

Nature Chemistry, Год журнала: 2017, Номер 9(11), С. 1043 - 1055

Опубликована: Окт. 16, 2017

Язык: Английский

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Organelle-targeting metal complexes: From molecular design to bio-applications

Coordination Chemistry Reviews, Год журнала: 2017, Номер 378, С. 66 - 86

Опубликована: Ноя. 6, 2017

Язык: Английский

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Recent Advances in the Development of Chromophore-Based Chemosensors for Nerve Agents and Phosgene

ACS Sensors, Год журнала: 2017, Номер 3(1), С. 27 - 43

Опубликована: Дек. 12, 2017

The extreme toxicity and ready accessibility of nerve agents phosgene has caused an increase in the demand to develop effective systems for detection these substances. Among traditional platforms utilized this purpose, chemosensors including surface acoustic wave (SAW) sensors, enzymes, carbon nanotubes, nanoparticles, chromophore based sensors have attracted increasing attention. In review, we describe a comprehensive manner recent progress that been made on development chromophore-based detecting (mimic) phosgene. This review comprises two sections focusing studies each sections, discussion follows format which concentrates different reaction sites/mechanisms involved sensing processes. Finally, uncovered efforts are compared with those other methods challenges facing design more discussed.

Язык: Английский

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Targeted Solvatochromic Fluorescent Probes for Imaging Lipid Order in Organelles under Oxidative and Mechanical Stress

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(2), С. 912 - 924

Опубликована: Янв. 8, 2021

Biomembranes constitute a basis for all compartments of live cells, and therefore, the monitoring their lipid organization is essential understanding cell status activity. However, sensing imaging specifically in different organelles cells remain challenging. Here, we designed an array solvatochromic probes based on Nile Red bearing ligands specific targeting endoplasmic reticulum, mitochondria, lysosomes, Golgi apparatus, plasma membranes, droplets. These polarity-sensitive detected variations order by changing emission maximum, as evidenced fluorescence spectroscopy model membranes. In colocalization microscopy experiments with reference organelle markers, they exhibited good selectivity. Using two-color microscopy, new enabled local polarity cells. To exclude biased effect probe design sensitivity to membrane properties, calibrated membranes under microscope, which first quantitative description each interest. Cholesterol extraction/enrichment confirmed capacity sense order, revealing that poor cholesterol are particularly affected its enrichment. The also revealed oxidative mechanical stresses produced changes were characteristic organelle, mitochondria lysosomes being stress sensitive. powerful toolbox response physical chemical stimuli at level individual organelles, remains underexplored direction cellular research.

Язык: Английский

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Simultaneous Two-Color Visualization of Lipid Droplets and Endoplasmic Reticulum and Their Interplay by Single Fluorescent Probes in Lambda Mode

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(8), С. 3169 - 3179

Опубликована: Фев. 11, 2021

In living systems, subcellular organelles mutually cooperate and closely contact to form organelle interaction networks. Thus, the simultaneous discriminative visualization of different is extremely valuable for elucidating their distribution interplay. However, such meaningful investigations remain a great challenge due lack advanced single fluorescent probes (SF-probes) capable two-color imaging two targets. Herein, first time, we present excited-state intramolecular proton transfer (ESIPT) based SF-probes (PPC EPC) fluorescence lipid droplets (LDs) endoplasmic reticulum (ER) under single-wavelength excitation. Due strong electron-donating ability side substituents, spectra colors these ESIPT are highly sensitive nuance water contents between LDs ER, leading orange green in respectively, Lambda mode. Using probe PPC or EPC, morphology, size, ER have been investigated live cells tissues. With aid situ real-time mode, observed generation newborn near regions close apposition shared identical colors, probably providing proof mainstream hypothesis that originate from ER. The remarkable performances render as powerful tools decipher LD-ER related biological processes.

Язык: Английский

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