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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New Designs for Phototherapeutic Transition Metal Complexes

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(1), С. 61 - 73

Опубликована: Июль 16, 2019

Abstract In this Minireview, we highlight recent advances in the design of transition metal complexes for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT), discuss challenges opportunities translation such agents into clinical use. New designs light‐activated offer photoactivatable prodrugs with novel targeted mechanisms action. Light irradiation can provide spatial temporal control drug activation, increasing selectivity reducing side‐effects. The photophysical photochemical properties be controlled by appropriate choice metal, its oxidation state, number types ligands, coordination geometry.

Язык: Английский

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An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(9), С. 4657 - 4665

Опубликована: Ноя. 21, 2020

Immunogenic cell death (ICD) is a vital component of therapeutically induced anti-tumor immunity. An iridium(III) complex (Ir1), containing an N,N-bis(2-chloroethyl)-azane derivate, as endoplasmic reticulum-localized ICD inducer for non-small lung cancer (NSCLC) reported. The characteristic discharge damage-associated molecular patterns (DAMPs), that is, surface exposure calreticulin (CRT), extracellular exclusion high mobility group box 1 (HMGB1), and ATP, were generated by Ir1 in A549 cells, accompanied increase reticulum stress reactive oxygen species (ROS). vaccination immunocompetent mice with Ir1-treated dying cells elicited antitumor CD8+ T response Foxp3+ depletion, which eventually resulted long-acting immunity the activation cells. first Ir-based capable developing immunomodulatory immunogenic death.

Язык: Английский

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Smart Design of Nanomaterials for Mitochondria‐Targeted Nanotherapeutics

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(5), С. 2232 - 2256

Опубликована: Март 4, 2020

Mitochondria are the powerhouse of cells. They vital organelles that maintain cellular function and metabolism. Dysfunction mitochondria results in various diseases with a great diversity clinical appearances. In past, strategies have been developed for fabricating subcellular-targeting drug-delivery nanocarriers, enabling internalization subsequent organelle localization. Of late, innovative emerged smart design multifunctional nanocarriers. Hierarchical targeting enables nanocarriers to evade overcome barriers encountered upon vivo administration reach good bioavailability. Stimuli-responsive allow controlled release therapeutics occur at desired target site. Synergistic therapy can be achieved using combination approaches such as chemotherapy, gene phototherapy. this Review, we survey field recent developments used mitochondria-targeted therapeutics. Existing challenges unexplored therapeutic opportunities also highlighted discussed inspire next generation mitochondrial-targeting nanotherapeutics.

Язык: Английский

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A Multi‐action and Multi‐target Ru^II–Pt^IV Conjugate Combining Cancer‐Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(18), С. 7069 - 7075

Опубликована: Фев. 4, 2020

Abstract Pt II complexes are commonly used to treat cancer. To reduce their side effects and improve pharmacological properties, IV being developed as prodrug candidates that activated by reduction in cancer cells. Concomitantly, Ru polypyridine have gained much attention photosensitizers for use photodynamic therapy due attractive characteristics. In this article, a novel –Ru conjugate, which combines chemotherapy with PDT, is presented. Upon entering the cell, centre reduced axial ligands including complex phenylbutyrate released. As each component has its individual targets, conjugate exerts multi‐target multi‐action effect (photo‐)cytotoxicity values upon irradiation up 595 nm low nanomolar range various (drug resistant) 2D monolayer cells 3D multicellular tumour spheroids.

Язык: Английский

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Boosting Cancer Therapy with Organelle-Targeted Nanomaterials

ACS Applied Materials & Interfaces, Год журнала: 2019, Номер 11(30), С. 26529 - 26558

Опубликована: Май 28, 2019

The ultimate goal of cancer therapy is to eliminate malignant tumors while causing no damage normal tissues. In the past decades, numerous nanoagents have been employed for treatment because their unique properties over traditional molecular drugs. However, lack selectivity and unwanted therapeutic outcomes severely limited index nanodrugs. Recently, a series nanomaterials that can accumulate in specific organelles (nucleus, mitochondrion, endoplasmic reticulum, lysosome, Golgi apparatus) within cells received increasing interest. These rationally designed either directly destroy subcellular structures or effectively deliver drugs into proper targets, which further activate certain cell death pathways, enabling them boost efficiency, lower drug dosage, reduce side effects, avoid multidrug resistance, prevent recurrence. this Review, design principles, targeting strategies, mechanisms, current challenges, potential future directions organelle-targeted will be introduced.

Язык: Английский

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Recent advances in the development of responsive probes for selective detection of cysteine

Coordination Chemistry Reviews, Год журнала: 2020, Номер 408, С. 213182 - 213182

Опубликована: Янв. 25, 2020

Язык: Английский

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Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(14), С. 6578 - 6587

Опубликована: Март 14, 2020

The utilization of photodynamic therapy (PDT) for the treatment various types cancer has gained increasing attention over last decades. Despite clinical success approved photosensitizers (PSs), their application is sometimes limited due to poor water solubility, aggregation, photodegradation, and slow clearance from body. To overcome these drawbacks, research efforts are devoted toward development metal complexes especially Ru(II) polypyridine based on attractive photophysical biological properties. recent developments, vast majority utilize blue or UV-A light obtain a PDT effect, limiting penetration depth inside tissues and, therefore, possibility treat deep-seated large tumors. circumvent we present first example DFT guided search efficient PSs with substantial spectral red shift window. Thanks this design, have unveiled complex that causes phototoxicity in very low micromolar nanomolar range at clinically relevant 595 nm, monolayer cells as well 3D multicellular tumor spheroids.

Язык: Английский

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Photodecaging of a Mitochondria-Localized Iridium(III) Endoperoxide Complex for Two-Photon Photoactivated Therapy under Hypoxia

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(9), С. 4091 - 4101

Опубликована: Фев. 16, 2022

Despite the clinical success of photodynamic therapy (PDT), application this medical technique is intrinsically limited by low oxygen concentrations found in cancer tumors, hampering production therapeutically necessary singlet (1O2). To overcome limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (2-O-IrAn), which, upon two-photon irradiation NIR, synergistically releases highly cytotoxic complex (2-IrAn), oxygen, and an alkoxy radical. 2-O-IrAn was to be (photo-)toxic hypoxic tumor cells multicellular spheroids (MCTS) nanomolar range. provide selectivity improve pharmacological properties 2-O-IrAn, it encapsulated into biotin-functionalized polymer. The generated nanoparticles were nearly fully eradicate inside mouse model within single treatment. This study presents, best our knowledge, first example iridium(III)-based for synergistic therapy/photoactivated chemotherapy, opening up new avenues treatment tumors.

Язык: Английский

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In‐vitro and In‐vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(17), С. 9474 - 9479

Опубликована: Янв. 15, 2021

Abstract Photocatalytic anticancer profile of a Ir III photocatalyst ( Ir3 ) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported. showed selective photo‐cytotoxicity against cisplatin‐ sorafenib‐resistant cell lines while remaining dormant to normal in the dark. exhibited photo‐catalytic oxidation cellular co‐enzyme, reduced nicotinamide adenine dinucleotide phosphate (NADPH), amino acids via single electron transfer mechanism. The photo‐induced intracellular redox imbalance change mitochondrial membrane potential resulted necrosis apoptosis cancer cells. Importantly, efficiency as evident from vivo zebrafish mouse models. To best our knowledge, first based such photocatalytic therapeutic effect.

Язык: Английский

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