Luminescent and Photofunctional Transition Metal Complexes: From Molecular Design to Diagnostic and Therapeutic Applications

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(32), С. 14420 - 14440

Опубликована: Авг. 4, 2022

There has been emerging interest in the exploitation of photophysical and photochemical properties transition metal complexes for diagnostic therapeutic applications. In this Perspective, we highlight major recent advances development luminescent photofunctional complexes, particular, those rhenium(I), ruthenium(II), osmium(II), iridium(III), platinum(II), as bioimaging reagents phototherapeutic agents, with a focus on molecular design strategies that harness modulate interesting behavior complexes. We also discuss current challenges future outlook both fundamental research clinical

Язык: Английский

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Ruthenium-Based Photoactivated Chemotherapy

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(43), С. 23397 - 23415

Опубликована: Окт. 17, 2023

Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to undergo excited-state deactivation via photosubstitution reactions makes them quite unique in inorganic photochemistry. As consequence, they have been used, general, for building dynamic molecular systems responsive light but, more particularly, the field oncology, as prodrugs new cancer treatment modality called photoactivated chemotherapy (PACT). Indeed, coordination bond be selectively broken under visible irradiation offers fascinating perspectives oncology: it is possible make poorly toxic agents dark that become activated toward cell killing simple compound inside tumor. In this Perspective, we review most important concepts behind PACT idea, relationship between ruthenium compounds used those related phototherapeutic approach photodynamic therapy (PDT), discuss questions about real-life applications clinic. We conclude Perspective with challenges an outlook.

Язык: Английский

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A Metal‐Free Mesoporous Carbon Dots/Silica Hybrid Type I Photosensitizer with Enzyme‐Activity for Synergistic Treatment of Hypoxic Tumor

Advanced Functional Materials, Год журнала: 2023, Номер 33(25)

Опубликована: Март 10, 2023

Abstract As a less O 2 ‐dependent photodynamic therapy (PDT), type I PDT is an effective approach to overcome the hypoxia‐induced low efficiency against solid tumors. However, commonly used metal‐involved agents suffer from long‐term biosafety concern. Herein, metal‐free photosensitizer, N ‐doped carbon dots/mesoporous silica nanoparticles (NCDs/MSN, ≈40 nm) nanohybrid with peroxidase (POD)‐like activity for synergistic and enzyme‐activity treatment, developed on gram scale via facile one‐pot strategy through mixing source precursor assistance of template. Benefiting narrow bandgap (1.92 eV) good charge separation capacity NCDs/MSN, upon 640 nm light irradiation, excited electrons in conduction band can effectively generate •− by reduction dissolved one‐electron transfer process even under hypoxic conditions, inducing apoptosis tumor cells. Moreover, photoinduced partially transform into more toxic • OH two‐electron reduction. POD‐like NCDs/MSN catalyze endogenous H microenvironment, further synergistically ablating 4T1 Therefore, mass production way synthesize novel photosensitizer enzyme‐mimic treatment tumors provided, which exhibits promising clinical translation prospects.

Язык: Английский

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Type I Photosensitizer Targeting G‐Quadruplex RNA Elicits Augmented Immunity for Cancer Ablation

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(17)

Опубликована: Март 1, 2023

Type I photodynamic therapy (PDT) represents a promising treatment modality for tumors with intrinsic hypoxia. However, type photosensitizers (PSs), especially ones near infrared (NIR) absorption, are limited and their efficacy needs improvement via new targeting tactics. We develop NIR PS by engineering acridinium derived donor-π-acceptor systems. The exhibits an exclusive PDT mechanism due to effective intersystem crossing disfavored energy transfer O2 , shows selective binding G-quadruplexes (G4s) hydrogen bonds identified molecular docking study. Moreover, it enables fluorogenic detection of G4s efficient ⋅- production in hypoxic conditions, leading immunogenic cell death substantial variations gene expression RNA sequencing. Our strategy demonstrates augmented antitumor immunity ablation cold tumor, highlighting its potential RNA-targeted precision cancer therapy.

Язык: Английский

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Metallopolymer strategy to explore hypoxic active narrow-bandgap photosensitizers for effective cancer photodynamic therapy

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 2, 2024

Abstract Practical photodynamic therapy calls for high-performance, less O 2 -dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based exhibit excellent photocatalytic performance, but in vivo applications are hindered by conventional -dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy engineering iridium complexes exhibiting Type-I enhancing absorption intensity blue near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1 , where atom is covalently coupled polymer backbone, over 80 times higher than that its mother without under 680 nm irradiation. This also works effectively when directly included ( Ir-P2 ) backbones, wide generality. The nanoparticles efficient •− conjugated with integrin αvβ3 binding cRGD achieve targeted therapy.

Язык: Английский

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Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7360 - 7376

Опубликована: Фев. 15, 2025

Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance conventional therapies, leading poor patient outcomes. This challenges the efficiency photodynamic therapy (PDT), which relies on generation cytotoxic reactive oxygen species (ROS) through irradiation photosensitizer (PS), process partially dependent levels. In this work, we introduce novel family potent PSs based ruthenium(II) polypyridyl complexes with 2,2′-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY exhibit outstanding in vitro cytotoxicity against CT-26 cells when irradiated light within phototherapeutic window, achieving nanomolar potency both normoxic hypoxic conditions while remaining nontoxic dark, impressive phototoxic indices (>30,000). Their ability generate Type I II ROS underpins their exceptional PDT efficiency. The lead compound study, SCV49, shows favorable vivo pharmacokinetic profile, excellent toxicological tolerability, tumor growth inhibition mice bearing subcutaneous tumors at doses as low 3 mg/kg upon deep-red (660 nm). These results allow us propose SCV49 strong candidate for further preclinical development, particularly treating large tumors.

Язык: Английский

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Disruption of Zinc Homeostasis by a Novel Platinum(IV)‐Terthiophene Complex for Antitumor Immunity

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(8)

Опубликована: Дек. 22, 2022

Zinc homeostatic medicine is of great potential for cancer chemo-immunotherapy; however, there are few reports on antitumor compounds that can trigger Zn2+ -mediated immune responses. In this work, we developed a novel cyclometalated PtIV -terthiophene complex, Pt3, not only induces DNA damage and cellular metabolism dysregulation, but also disrupts zinc homeostasis as indicated by the abnormal transcriptional level regulatory proteins, excess accumulation in cytoplasm, down-regulation metallothioneins (MTs), which further caused redox imbalance. The simultaneous disruption response to Pt3 treatment activated gasdermin-D mediated pyroptosis accompanied cytoskeleton remodeling, thus releasing pro-inflammatory cytokines promote dendritic cell (DC) maturation T tumor-infiltration, eventually eliminating both primary distant tumors vivo. As far know, first metal complex regulate activate immunity.

Язык: Английский

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Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

Molecules, Год журнала: 2023, Номер 28(4), С. 1959 - 1959

Опубликована: Фев. 18, 2023

Since the accidental discovery of anticancer properties cisplatin more than half a century ago, significant efforts by broad scientific community have been and are currently being invested into search for metal complexes with antitumor activity. Coordination compounds transition metals such as platinum (Pt), ruthenium (Ru) gold (Au) proven their effectiveness diagnostic and/or antiproliferative agents. In recent years, experimental work on potential applications elements including lanthanum (La) post-transition gallium (Ga) in field oncology has gaining traction. The authors present review article aim to help reader “catch up” some latest developments vast subject coordination oncology. Herewith is offered published literature Pt, Ru, Au, Ga La that released over past three years hope readers find following informative helpful.

Язык: Английский

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Ir(III) Half-Sandwich Photosensitizers with a π-Expansive Ligand for Efficient Anticancer Photodynamic Therapy

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(3), С. 1783 - 1811

Опубликована: Янв. 31, 2024

One approach to reduce the side effects of chemotherapy in cancer treatment is photodynamic therapy (PDT), which allows spatiotemporal control cytotoxicity. We have used strategy coordinating π-expansive ligands increase excited state lifetimes Ir(III) half-sandwich complexes order facilitate generation 1O2. obtained derivatives formulas [Cp*Ir(C∧N)Cl] and [Cp*Ir(C∧N)L]BF4 with different degrees π-expansion C∧N ligands. Complexes more ligand are very effective photosensitizers phototoxic indexes PI > 2000. Furthermore, values 63 were achieved red light. Time-dependent density functional theory (TD-DFT) calculations nicely explain effect π-expansion. The produce reactive oxygen species (ROS) at cellular level, causing mitochondrial membrane depolarization, cleavage DNA, nicotinamide adenine dinucleotide (NADH) oxidation, as well lysosomal damage. Consequently, cell death by apoptosis secondary necrosis activated. Thus, we describe first class iridium cyclometalated active PDT.

Язык: Английский

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Bithiophene‐Functionalized Infrared Two‐Photon Absorption Metal Complexes as Single‐Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(27)

Опубликована: Апрель 24, 2024

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, chemotherapy. The significant two-photon absorption at 808 nm remarkable singlet oxygen superoxide anion production in aqueous solution cells when exposed to infrared irradiation. most potent Ru(II) complex Ru7 enters tumor via the rare macropinocytosis, locates both nuclei mitochondria, regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase RNA polymerase inhibition their effects photoactivated apoptosis, ferroptosis cleavage. exhibits high efficacy vivo malignant melanoma cisplatin-resistant non-small cell lung cancer tumors, a 100 % survival rate of mice, low toxicity normal residual rate. Such an activatable metal may contribute new generation single-molecule-based integrated diagnosis treatment address drug resistance clinical practice phototherapy large, deeply located solid tumors.

Язык: Английский

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