An NIR‐II Excitable AIE Small Molecule with Multimodal Phototheranostic Features for Orthotopic Breast Cancer Treatment

Advanced Materials, Год журнала: 2024, Номер 36(14)

Опубликована: Янв. 2, 2024

One-for-all phototheranostics, referring to a single component simultaneously exhibiting multiple optical imaging and therapeutic modalities, has attracted significant attention due its excellent performance in cancer treatment. Benefitting from the superiority balancing diverse competing energy dissipation pathways, aggregation-induced emission luminogens (AIEgens) are proven be ideal templates for constructing one-for-all multimodal phototheranostic agents. However, this knowledge, all-round AIEgens that can triggered by second near-infrared (NIR-II, 1000-1700 nm) light have not been reported. Given deep tissue penetration high maximum permissible exposure of NIR-II excitation light, herein, work reports first time an laser excitable AIE small molecule (named BETT-2) with features taking full use advantage molecule-facilitated versatility as well synchronously maximizing molecular donor-acceptor strength conformational distortion. As formulated into nanoparticles (NPs), BETT-2 NPs light-driven fluorescence-photoacoustic-photothermal trimodal imaging-guided photodynamic-photothermal synergistic therapy orthotopic mouse breast tumors is fully demonstrated systematic vitro vivo evaluations. This offers valuable insights developing activatable systems.

Язык: Английский

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Viscosity-responsive NIR-II fluorescent probe with aggregation-induced emission features for early diagnosis of liver injury

Biomaterials, Год журнала: 2023, Номер 300, С. 122190 - 122190

Опубликована: Июнь 8, 2023

Язык: 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, Год журнала: 2024, Номер 146(13), С. 8991 - 9003

Опубликована: Март 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.

Язык: Английский

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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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Thiophene π‐Bridge Manipulation of NIR‐II AIEgens for Multimodal Tumor Phototheranostics

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Фев. 12, 2024

Abstract The fabrication of a multimodal phototheranostic platform on the basis single‐component theranostic agent to afford both imaging and therapy simultaneously, is attractive yet full challenges. emergence aggregation‐induced emission luminogens (AIEgens), particularly those emit fluorescence in second near‐infrared window (NIR‐II), provides powerful tool for cancer treatment by virtue adjustable pathway radiative/non‐radiative energy consumption, deeper penetration depth aggregation‐enhanced performance. Although bulky thiophene π‐bridges such as ortho ‐alkylated thiophene, 3,4‐ethoxylene dioxythiophene benzo[ c ]thiophene are commonly adopted construct NIR‐II AIEgens, subtle differentiation their behaviours has be comprehensively investigated. In this work, systematical investigations discovered that AIEgen BT‐NS bearing possesses acceptable intensity, efficient reactive oxygen species generation, high photothermal conversion efficiency. Eventually, using nanoparticles, unprecedented performance fluorescence/photoacoustic/photothermal imaging‐guided synergistic photodynamic/photothermal elimination tumors was demonstrated. This study thus offers useful insights into developing versatile systems clinical trials.

Язык: Английский

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De Novo Designed Ru(II) Metallacycle as a Microenvironment‐Adaptive Sonosensitizer and Sonocatalyst for Multidrug‐Resistant Biofilms Eradication

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(15)

Опубликована: Фев. 8, 2024

Abstract Albeit sonodynamic therapy (SDT) has achieved encouraging progress in microbial sterilization, the scarcity of guidelines for designing highly effective sonosensitizers and intricate biofilm microenvironment (BME), substantially hamper therapeutic efficacy against infections. To address bottlenecks, we innovatively design a Ru(II) metallacycle‐based sonosensitizer/sonocatalyst (named Ru‐A3‐TTD ) to enhance potency sonotherapy by employing molecular engineering strategies tailored BME. Our approach involves augmenting ’s production ultrasonic‐triggered reactive oxygen species (ROS), surpassing performance commercial sonosensitizers, through straightforward but potent π‐expansion approach. Within BME, synergistically amplifies sonotherapeutic via triple‐modulated approaches: (i) alleviation hypoxia, leading increased ROS generation, (ii) disruption antioxidant defense system, which shields from glutathione consumption, (iii) enhanced penetration, enabling deep sites. Notably, sono‐catalytically oxidizes NADPH, critical coenzyme involved defenses. Consequently, demonstrates superior eradication multidrug‐resistant Escherichia coli compared conventional clinical antibiotics, both vitro vivo. our knowledge, this study represents pioneering instance supramolecular sonosensitizer/sonocatalyst. It provides valuable insights into structure‐activity relationship paves promising pathway treatment

Язык: Английский

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Strategies to address key challenges of metallacycle/metallacage-based supramolecular coordination complexes in biomedical applications

Chemical Society Reviews, Год журнала: 2024, Номер 53(6), С. 3167 - 3204

Опубликована: Янв. 1, 2024

We report strategies employed by metallacycle/metallacage-based supramolecular coordination complexes to enhance water solubility and biostability reduce potential toxicity side effects for biomedical applications.

Язык: Английский

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An All‐Rounder for NIR‐II Phototheranostics: Well‐Tailored 1064 nm‐Excitable Molecule for Photothermal Combating of Orthotopic Breast Cancer

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(26)

Опубликована: Апрель 19, 2024

The second near-infrared (NIR-II, 1000-1700 nm) light-activated organic photothermal agent that synchronously enables satisfying NIR-II fluorescence imaging is highly warranted yet rather challenging on the basis of overwhelming nonradiative decay. Herein, such an agent, namely TPABT-TD, was tactfully designed and constructed via employing benzo[c]thiophene moiety as bulky electron donor/π-bridge tailoring peripheral molecular rotors. Benefitting from its high donor-acceptor strength finely modulated intramolecular motion, TPABT-TD simultaneously exhibits ultralong absorption in region, intense emission NIR-IIa (1300-1500 region nanoaggregates, conversion upon 1064 nm laser irradiation. Those intrinsic advantages endow nanoparticles with prominent fluorescence/photoacoustic/photothermal trimodal imaging-guided therapy against orthotopic 4T1 breast tumor negligible adverse effect.

Язык: Английский

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NIR‐II Excitable Semiconducting Polymers with AIE Characteristics for Fluorescence‐Photoacoustic Imaging‐Guided Synergistic Phototherapy

Advanced Functional Materials, Год журнала: 2024, Номер 34(32)

Опубликована: Март 22, 2024

Abstract The development of semiconducting polymers (SPs) with simultaneous second near‐infrared (NIR‐II) absorption and multimodal phototheranostic functions is highly desired in the field oncotherapy. Aggregation‐induced emission luminogens (AIEgens) have been acknowledged to possess unique potential integrating multiple diagnostic therapeutic modalities into one organic molecule. Nevertheless, SPs are hard achieve AIE activity due their extended π‐conjugated skeletons as well large planar configuration commonly‐used electrophilic acceptor moieties. Herein, an ingenious dimerization‐based distortion strategy proposed current work by taking advantage sterically encumbered acceptors structure for successful construction AIE‐active SPs. Through further finely adjusting molecular donor–acceptor interaction strength, obtained named SP3 bearing highest intramolecular charge transfer effect presented NIR‐II aggregation‐induced fluorescence emission, good reactive oxygen species production ability, superior photothermal conversion performance. Accordingly, selected fabricate nanoparticles successfully applied laser‐triggered fluorescence‐photoacoustic imaging‐guided photodynamic‐photothermal therapy tumors. This study represents first excitable SP, offers a new perspective on designing advanced efficient treatment malignant tumor.

Язык: Английский

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2, 1, 3‐Benzothiadiazole Derivative Small Molecule Fluorophores for NIR‐II Bioimaging

Advanced Functional Materials, Год журнала: 2024, Номер 34(16)

Опубликована: Янв. 4, 2024

Abstract Second near‐infrared (NIR‐II) bioimaging technology shows broad application prospects in the field of biomedical due to its significant superiority deep tissue penetration and high signal‐to‐background ratio. Among them, organic small molecule fluorophores have received progressively more consideration their low biotoxicity, biocompatibility, rapid clearance, good modification properties. As key acceptor core, 2, 1, 3‐benzothiadiazole (BTD) derivative plays an essential role construction donor‐acceptor‐donor type NIR‐II fluorophores. This mini‐review summarizes research development based on BTD derivatives bioimaging, focusing molecular design photophysical properties, introduces a part applications biological field. Furthermore, challenges BTD‐based future are discussed .

Язык: Английский

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