Fluorescent dyes based on rhodamine derivatives for bioimaging and therapeutics: recent progress, challenges, and prospects

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(16), P. 5607 - 5651

Published: Jan. 1, 2023

Since their inception, rhodamine dyes have been extensively applied in biotechnology as fluorescent markers or for the detection of biomolecules owing to good optical physical properties. Accordingly, they emerged a powerful tool visualization living systems. In addition fluorescence bioimaging, molecular design derivatives with disease therapeutic functions (e.g., cancer and bacterial infection) has recently attracted increased research attention, which is significantly important construction libraries diagnostic integration. However, reviews focusing on integrated strategies dye-based diagnosis treatment wide application are extremely rare. this review, first, brief history development dyes, transformation from bioimaging therapy, concept optics-based integration its significance human presented. Next, systematic review several excellent rhodamine-based well treatment, Finally, challenges practical future outlook clinical translation also discussed.

Language: Английский

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Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(13), P. 4392 - 4442

Published: Jan. 1, 2023

Metal agents have made incredible strides in preclinical research and clinical applications, but their short emission/absorption wavelengths continue to be a barrier distribution, therapeutic action, visual tracking, efficacy evaluation.

Language: Английский

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Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Language: Английский

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Bioorthogonal Disruption of Pyroptosis Checkpoint for High-Efficiency Pyroptosis Cancer Therapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16658 - 16668

Published: July 24, 2023

Pyroptosis is an inflammatory form of programmed cell death that holds great promise in cancer therapy. However, autophagy as the crucial pyroptosis checkpoint and self-protective mechanism cells significantly weakens therapeutic efficiency. Here, a bioorthogonal nanoregulator constructed to induce disrupt checkpoint, enabling high-efficiency The allows situ synthesis accumulation photosensitizer PpIX mitochondria directly produce mitochondrial ROS, thus triggering pyroptosis. Meanwhile, generated inhibitor via palladium-catalyzed chemistry can boost efficacy. With biomimetic membrane coating, this platform for modulating presents specificity poses no harm normal tissue, resulting highly efficient safe antitumor treatment. To our knowledge, first report on disrupting intrinsic protective tumor This work highlights plays key regulative role therapy, which would motivate future design regimens.

Language: Английский

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Activation of Pyroptosis Using AIEgen-Based sp² Carbon-Linked Covalent Organic Frameworks

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(32), P. 17689 - 17699

Published: Aug. 8, 2023

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect apoptosis resistance often limit therapeutic efficacy. Herein, we demonstrated first time that linking luminogens with aggregation-induced emission (AIEgens) into COF networks via vinyl linkages was an effective strategy construct nonmetallic pyroptosis inducers boosting antitumor immunity. Mechanistic investigations revealed formation linkage in AIE endowed it not only high brightness but also strong absorption ability, long lifetime, quantum yield favor generation reactive oxygen species eliciting pyroptosis. In addition, synergized system αPD-1 effectively eradicated primary distant tumors inhibited tumor recurrence metastasis bilateral 4T1 model.

Language: Английский

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Engineering Au₄₄ Nanoclusters for NIR-II Luminescence Imaging-Guided Photoactivatable Cancer Immunotherapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(16), P. 15605 - 15614

Published: July 28, 2023

Immunotherapy is an advanced therapeutic strategy of cancer treatment but suffers from the issues off-target adverse effects, lack real-time monitoring techniques, and unsustainable response. Herein, ultrasmall Au nanocluster (NC)-based theranostic probe designed for second near-infrared window (NIR-II) photoluminescence (PL) imaging-guided phototherapies photoactivatable immunotherapy. The (Au44MBA26-NLG short) composed atomically precise NIR-II emitting Au44MBA26 NCs (here MBA denotes water-soluble 4-mercaptobenzoic acid) conjugated with immune checkpoint inhibitor 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol (NLG919) via a singlet oxygen (1O2)-cleavable linker. Upon NIR photoirradiation, Au44MBA26-NLG not only enables PL imaging tumors in deep tissues guiding tumor therapy also allows leverage photothermal property (PTT) photogenerated 1O2 photodynamic (PDT) releasing NLG919 Such multiple effect modulated by prompts proliferation activation effector T cells, upshifts systemic antitumor T-lymphocyte (T cell) immunity, finally suppresses growth both primary distant living mice. Overall, this study may provide promising nanoplatform toward

Language: Английский

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Augmenting Cancer Therapy with a Supramolecular Immunogenic Cell Death Inducer: A Lysosome-Targeted NIR-Light-Activated Ruthenium(II) Metallacycle

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8991 - 9003

Published: March 21, 2024

Though immunogenic cell death (ICD) has garnered significant attention in the realm of anticancer therapies, effectively stimulating strong immune responses with minimal side effects deep-seated tumors remains challenging. Herein, we introduce a novel self-assembled near-infrared-light-activated ruthenium(II) metallacycle, Ru1105 (λem = 1105 nm), as first example Ru(II) supramolecular ICD inducer. synergistically potentiates immunomodulatory and reduces adverse through multiple regulated approaches, including NIR-light excitation, increased reactive oxygen species (ROS) generation, selective targeting tumor cells, precision organelle localization, improved penetration/retention capabilities. Specifically, demonstrates excellent depth-activated ROS production (∼1 cm), resistance to diffusion, anti-ROS quenching. Moreover, exhibits promising results cellular uptake generation cancer cells multicellular spheroids. Importantly, induces more efficient an ultralow dose (10 μM) compared conventional agent, oxaliplatin (300 μM). In vivo experiments further confirm Ru1105's potency inducer, eliciting CD8+ T depleting Foxp3+ effects. Our research lays foundation for design secure exceptionally potent metal-based agents immunotherapy.

Language: Английский

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Mitochondria-Targeting Type-I Photodrug: Harnessing Caspase-3 Activity for Pyroptotic Oncotherapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9413 - 9421

Published: March 20, 2024

Precise control of cellular signaling events during programmed cell death is crucial yet challenging for cancer therapy. The modulation signal transduction in cells holds promise but limited by the lack efficient, biocompatible, and spatiotemporally controllable approaches. Here we report a photodynamic strategy that modulates both apoptotic pyroptotic altering caspase-3 protein activity associated crosstalk. This employs mitochondria-targeting, near-infrared activatable probe (termed M-TOP) functions via type-I photochemical mechanism. M-TOP less dependent on oxygen more effective treating drug-resistant cells, even under hypoxic conditions. Our study shows higher doses induce caspase-3/gasdermin-E pathway, whereas lower lead to apoptosis. method across diverse gasdermin-E-expressing cells. Moreover, mediated shift from can evoke controlled inflammatory response, leading robust balanced immune reaction. effectively inhibits distal tumor growth postsurgical recurrence. work demonstrates feasibility modulating intracellular through rational design anticancer drugs.

Language: Английский

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Zinc–Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(15), P. 10542 - 10556

Published: April 1, 2024

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of tumors strongly reduce sensitivity to immunotherapy. To sensitize patients immunotherapy, hyaluronic acid-modified zinc peroxide–iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized remodel increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade acid (HA) in extracellular matrix (ECM), thereby reshaping enhancing blood perfusion, drug penetration, immune cell infiltration. Furthermore, not only triggers pyroptosis through activation caspase-1/GSDMD-dependent pathway but also induces ferroptosis various mechanisms, including increasing levels Fe2+ intracellular iron pool, downregulating expression FPN1 inhibit efflux, activating p53 signaling cause failure SLC7A11-GSH-GPX4 axis. Upon treatment with FZOH, 4T1 cells undergo both pyroptosis, exhibiting strong immunogenic response. remodeling response induced by collectively compensate limitations immunotherapy significantly enhance antitumor checkpoint inhibitor αPD-1. This study proposes perspective therapy cancer.

Language: Английский

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Photoactivation Inducing Multifunctional Coupling of Fluorophore for Efficient Tumor Therapy In Situ

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(23)

Published: Feb. 15, 2024

Abstract Photoactivatable molecules, with high‐precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor ( BI ) is described that can be triggered by broad excitation light (405–660 nm), which further undergoes intersystem crossing H‐atom transfer processes to forming superoxide anion radicals (O 2 −• carbon radicals. Particularly, photoinduced gain carbon‐centered BI• allows for radical‐radical coupling afford combined crosslink product BI─BI ), would oxidized in presence O produce an extended conjugate system near infrared emission (820 nm). Besides, photochemically generated Cy─BI possesses ultra‐high photothermal conversion efficiency up 90.9%, optimized potential. What′s more, Western Blot assay reveals both photoproduct efficiently inhibit expression CHK1, irradiation induces apoptosis ultimately enhances phototherapeutic effects. Thus, combination cell cycle block inducing apoptosis, photodynamic therapy treatments significantly suppress solid tumor vivo antitumor efficacy explorations. This a novel finding developing as well applicability photoimaging tumor‐related areas.

Language: Английский

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