Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy

Chemical Science, Год журнала: 2023, Номер 14(11), С. 2901 - 2909

Опубликована: Янв. 1, 2023

Although metallacycle-based photosensitizers have attracted increasing attention in biomedicine, their clinical application has been hindered by inherent dark toxicity and unsatisfactory phototherapeutic efficiency. Herein, we employ a π-expansion strategy for ruthenium acceptors to develop series of Ru(ii) metallacycles (Ru1-Ru4), while simultaneously reducing enhancing phototoxicity, thus obtaining high phototoxicity index (PI). These enable deep-tissue (∼7 mm) fluorescence imaging reactive oxygen species (ROS) production exhibit remarkable anti-tumor activity even under hypoxic conditions. Notably, Ru4 the lowest toxicity, highest ROS generation ability an optimal PI (∼146). Theoretical calculations verify that exhibits largest steric bulk singlet-triplet energy gap (ΔEST, 0.62 eV). In vivo studies confirm allows effective safe phototherapy against A549 tumors. This work is expected open new avenue design high-performance metal-based potential applications.

Язык: Английский

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Enhancing Fractionated Cancer Therapy: A Triple-Anthracene Photosensitizer Unleashes Long-Persistent Photodynamic and Luminous Efficacy

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(9), С. 6252 - 6265

Опубликована: Фев. 20, 2024

Conventional photodynamic therapy (PDT) is often limited in treating solid tumors due to hypoxic conditions that impede the generation of reactive oxygen species (ROS), which are critical for therapeutic efficacy. To address this issue, a fractionated PDT protocol has been suggested, wherein light irradiation administered stages separated by dark intervals permit recovery during these breaks. However, current photosensitizers used incapable sustaining ROS production intervals, leading suboptimal outcomes (Table S1). circumvent drawback, we have synthesized novel photosensitizer based on triple-anthracene derivative designed prolonged generation, even after cessation exposure. Our study reveals unique action derivatives, facilitating direct and effective disruption biomolecules significantly improving efficacy S2). Moreover, existing lack imaging capabilities monitoring, constraints fine-tuning parameters also serves as an afterglow agent, emitting sustained luminescence postirradiation. This function allows precise optimization between sessions aids determining timing subsequent irradiation, thus enabling meticulous control over parameters. Utilizing our photosensitizer, formulated regimen effectively eliminates orthotopic pancreatic tumors. investigation highlights promise employing long-persistent activity advanced approaches overcome limitations tumor treatment.

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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Recent advances in the metal/organic hybrid nanomaterials for cancer theranostics

Coordination Chemistry Reviews, Год журнала: 2024, Номер 504, С. 215654 - 215654

Опубликована: Янв. 20, 2024

Язык: Английский

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Endoplasmic Reticulum‐Targeting Iridium(III) Nanosonosensitizer Amplifies Immunogenic Cell Death for Boosted Tumor Sono‐Immunotherapy

Advanced Functional Materials, Год журнала: 2024, Номер 34(26)

Опубликована: Фев. 27, 2024

Abstract Reactive oxygen species (ROS)‐induced endoplasmic reticulum (ER) stress in sonodynamic therapy (SDT) can elicit immunogenic cell death (ICD)‐initiated antitumor immunity for augmented sono‐immunotherapy. However, unsatisfactory activity and mediocre ER induction ability of sonosensitizers essentially restrict SDT efficacy ICD stimulation. Herein, a versatile ER‐targeting Iridium(III) nanosonosensitizer is developed as superior inducer boosted tumor An ingenious cholic acid (CA)‐functionalized sonosensitizer Ir‐CA well‐designed skillfully crosslinked with human serum albumin (HSA) to form HSA@Ir‐CA. With high stability, favorable tumor‐targeting ability, reduction‐responsiveness, HSA@Ir‐CA preferentially accumulates sites enhanced cellular uptake, followed by rapid disassembly responding intracellular reductive environment. The uncaged selectively accumulate precisely disrupt situ produced type I II ROS upon US irradiation high‐efficiency SDT. Moreover, the maximized eminently amplifies evoke robust systemic immunity, inhibiting growths primary/distant tumor, lung metastasis, recurrence. This combined immune checkpoint inhibitor (αPD‐L1) further achieves reinforced therapeutic outcome against immunologically “cold” tumor. study presents an effective paradigm optimize amplify ICD‐initiated responses

Язык: Английский

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A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Авг. 21, 2024

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation photosensitizers (PSs), many PSs lack specific subcellular targets are limited to first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy essential for strategies. Here, we synthesized four molecules with varying benzene ring numbers thiopyrylium structures preliminarily explore their properties. The near-infrared-II (NIR-II) PS Z1, higher count, exhibited superior ROS generation mitochondria-targeting abilities, large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high (especially type-I ROS) upon 808 nm laser irradiation, leading efficient mitochondria dysfunction combined apoptosis. Moreover, they exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) photoacoustic (PAI). Furthermore, NPs-mediated effectively inhibited growth minimal adverse effects. Our findings offer promising strategy therapy, warranting further preclinical investigations PDT.

Язык: Английский

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Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms action to combat resistance current therapy. We highlight recent progress in design platinum, ruthenium, iridium, gold other transition complexes, especially for applications as anticancer anti‐infective agents. In particular, understanding excited state chemistry related identification bioactive species (excited metallomics/pharmacophores) is important. metallodrugs are classified here photocatalysts, photorelease agents ligand‐activated Their activation wavelengths, cellular action, experimental theoretical metallomics states photoproducts discussed explore strategies investigation photoactivatable metallodrugs. These have potential clinical Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) Photothermal (PTT).

Язык: Английский

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Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy: novel insights and perspectives

Asian Journal of Pharmaceutical Sciences, Год журнала: 2023, Номер 18(4), С. 100829 - 100829

Опубликована: Июль 1, 2023

Current antitumor monotherapy has many limitations, highlighting the need for novel synergistic anticancer strategies. Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment. Photodynamic therapy (PDT) causes irreversible chemical damage to target lesions widely used therapy. However, PDT's effectiveness usually hindered by several obstacles, such as hypoxia, excess glutathione (GSH), tumor resistance. improves efficacy PDT increasing oxygen reactive species (ROS) or reducing GSH levels, also enhances ferroptosis induction due ROS effect microenvironment (TME). Strategies based on nanoparticles (NPs) can subtly exploit potential synergy PDT. This review explores recent advances current challenges landscape underlying mechanisms regulating PDT, well nano delivery system-mediated activity. These include polymers, biomimetic materials, metal organic frameworks (MOFs), inorganics, carrier-free NPs. Finally, we highlight future perspectives this emerging paradigm targeted cancer therapies.

Язык: Английский

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A chiral fluorescent Ir(iii) complex that targets the GPX4 and ErbB pathways to induce cellular ferroptosis

Chemical Science, Год журнала: 2023, Номер 14(5), С. 1114 - 1122

Опубликована: Янв. 1, 2023

Ferroptosis has recently emerged as a non-apoptotic form of programmed cell death and promising target for anticancer treatment. However, it is challenging to discover ferroptosis inducers with both highly selective tumour targeting low cytotoxicity normal cells. Here, we report an Ir(iii) complex, Ir1, that contains novel chiral pyridine RAS-selective lethal ligand (Py-RSL). This complex effectively inhibits glutathione peroxidase 4 (GPX4) suppressor protein 1 (FSP1) induce in human fibrosarcoma (HT-1080) Notably, metal coordination not only endows Ir1 fluorescent properties convenient cellular real-time tracking but also efficiently reduces the off-target toxicity Py-RSL ligand. Furthermore, label-free quantitative proteomic profiling revealed simultaneously ErbB signalling pathway enhance suppression. Our work first ferroptosis-inducing iridium dual mechanisms inhibition provides efficient route develop new metallodrugs.

Язык: Английский

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Durable organic nonlinear optical membranes for thermotolerant lightings and in vivo bioimaging

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 22, 2023

Abstract Organic nonlinear optical materials have potential in applications such as lightings and bioimaging, but tend to low photoluminescent quantum yields are prone lose the activity. Herein, we demonstrate weave large-area, flexible organic membranes composed of 4-N,N-dimethylamino-4ʹ-Nʹ-methyl-stilbazolium tosylate@cyclodextrin host-guest supramolecular complex. These exhibited a record high photoluminescence yield 73.5%, could continuously emit orange luminescence even being heated at 300 °C, thus enabling fabrication thermotolerant light-emitting diodes. The property these can be well-preserved polar environment. assemblies with multiphoton absorption characteristics were used for vivo real-time imaging Escherichia coli 1000 nm excitation. findings achieve scalable yields, good stability against thermal stress environment high-performance, durable optoelectronic devices humanized bio-probes.

Язык: Английский

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