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

Chemical Society Reviews, Год журнала: 2023, Номер 52(13), С. 4392 - 4442

Опубликована: Янв. 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.

Язык: Английский

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Engineered Metallacycle‐Based Supramolecular Photosensitizers for Effective Photodynamic Therapy

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(15)

Опубликована: Фев. 14, 2023

Abstract Although metallacycle‐based supramolecular photosensitizers (PSs) have attracted increasing attention in biomedicine, their clinical translation is still hindered by inherent dark toxicity. Herein, we report what to our knowledge the first example of a molecular engineering approach building blocks metallacycles for constructing series PSs ( RuA–RuD ), with aim simultaneously reducing toxicity and enhancing phototoxicity, consequently obtaining high phototoxicity indexes (PI). Detailed vitro investigations demonstrate that display cancer cellular uptake remarkable antitumor activity even under hypoxic conditions. Notably, RuD exhibited no displayed highest PI value (≈406). Theoretical calculations verified has largest steric hindrance lowest singlet‐triplet energy gap (Δ E ST , 0.61 eV). Further vivo studies confirmed allows safe effective phototherapy against A549 tumors.

Язык: Английский

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A Gas/phototheranostic Nanocomposite Integrates NIR‐II‐Peak Absorbing Aza‐BODIPY with Thermal‐Sensitive Nitric Oxide Donor for Atraumatic Osteosarcoma Therapy

Advanced Materials, Год журнала: 2023, Номер 35(35)

Опубликована: Апрель 20, 2023

Photothermal therapy (PTT) has received increasing interest in cancer therapeutics owing to its excellent efficacy and controllability. However, there are two major limitations PTT applications, which the tissue penetration depth of lasers within absorption range photothermal agents unavoidable empyrosis induced by high-energy lasers. Herein, a gas/phototheranostic nanocomposite (NA1020-NO@PLX) is engineered that integrates second near-infrared-peak (NIR-II-peak) absorbing aza-boron-dipyrromethenes (aza-BODIPY,NA1020) with thermal-sensitive nitric oxide (NO) donor (S-nitroso-N-acetylpenicillamine, SNAP). An enhanced intramolecular charge transfer mechanism proposed achieve NIR-II-peak absorbance (λmax = 1020 nm) on NA1020, thereby obtaining deep depth. The NA1020 exhibits remarkable conversion, making it feasible for deep-tissue orthotopic osteosarcoma providing favorable NIR-II emission precisely pinpoint tumor visible process. simultaneously investigated atraumatic therapeutic process an cell apoptosis indicates feasibility synergistic NO/low-temperature osteosarcoma. this strategy optimizes existing present repeatable tumors, validating potential clinical applications.

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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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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Tumor‐targeted nano‐adjuvants to synergize photomediated immunotherapy enhanced antitumor immunity

View, Год журнала: 2023, Номер 4(3)

Опубликована: Март 3, 2023

Abstract Photomediated immunotherapy explored to combine the anti‐cancer effect of phototherapy with immune enhancement ability immunotherapy, and shown great prospects for cancer treatment strategies. However, photomediated triggered antitumor immunity through release tumor antigens damage‐associated molecular patterns from necrotic cells was not enough mighty improve therapeutic benefits due immunosuppressive microenvironments. Herein, a tumor‐targeted nano‐adjuvant Fucoidan@Al(OH) 3 ‐Poly(I:C)/IR‐820 therapy metastasis inhibition designed prepared. The intrinsic immunomodulatory effects their simultaneously trigger antigen release, thereby reversing immunosuppression achieving potent augmented therapy, were explored. results proved that multifunctional combined photothermal, photodynamic, could effectively treat breast had by enhancing anti‐tumor immunomodulation, it should have application potential in cancer.

Язык: Английский

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Molecular Design of NIR-II Polymethine Fluorophores for Bioimaging and Biosensing

Chemical & Biomedical Imaging, Год журнала: 2023, Номер 1(3), С. 220 - 233

Опубликована: Май 18, 2023

Organic polymethine fluorophores with emission in the NIR-II window (1000–1700 nm) are receiving enormous attention biomolecular medicine and bioimaging, attributed to high absorption coefficients, bright emission, excellent biocompatibility, molecule adjustability. Recently, researchers have devoted significant effort designing improving making notable progress fluorescence imaging performance. This review summarizes recent developments molecular engineering design mentality of probes highlights their extensive bioimaging biosensing applications. Furthermore, we elucidate potential challenges perspectives these dyes chemical biomedicine imaging, which may stimulate further development high-performance dye contrast agents for future clinical

Язык: Английский

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Role of LGMN in tumor development and its progression and connection with the tumor microenvironment

Frontiers in Molecular Biosciences, Год журнала: 2023, Номер 10

Опубликована: Фев. 7, 2023

Legumain (LGMN) has been demonstrated to be overexpressed not just in breast, prostatic, and liver tumor cells, but also the macrophages that compose microenvironment. This supports idea LGMN is a pivotal protein regulating development, invasion, dissemination. Targeting with siRNA or chemotherapeutic medicines peptides can suppress cancer cell proliferation culture reduce growth vivo. Furthermore, legumain used as marker for detection targeting due its expression being significantly lower normal cells compared tumors tumor-associated (TAMs). Tumor formation influenced by aberrant of proteins alterations cellular architecture, microenvironment crucial deciding factor. an vivo-active cysteine protease catalyzes degradation numerous proteins. Its precise biological mechanism encompasses number routes, including effects on macrophage neovascular endothelium The purpose this work establish rationale thoroughly investigating function discovering novel early diagnosis markers therapeutic targets reviewing genesis progression relationship milieu.

Язык: Английский

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Aggregation‐induced emission artificial enzyme (AIEzyme) with DNase‐like activity: Imaging and matrix cleavage for combating bacterial biofilm

Aggregate, Год журнала: 2023, Номер 4(5)

Опубликована: Май 25, 2023

Abstract DNase‐catalyzed hydrolysis of extracellular DNA (eDNA) has been widely employed to eradicate intractable biofilms. Although aggregation‐induced emission (AIE) become the ideal tool for killing planktonic bacteria, AIE luminogens (AIEgens) often lack DNase‐mimetic activity, so as suffer from poor anti‐biofilm capacity. Here, an “AIEzyme”, a kind nanomaterial with enzyme‐like is designed and synthesized, where AIEgens are used ligands Zr‐based coordination polymer nanoparticles. Not only does AIEzyme have enduring activity low activation energy, but also structural rigidity‐stabilized fluorescence. Due long‐acting eDNA in biofilm, can efficiently disorganize established biofilms good penetrability realize healing superbug‐infected wounds under one dose AIEzyme. This work provides strategy endow ordinary DNase‐like activities. Moreover, AIEzymes be observed by virtue their own character, facilitating study on self‐positioning residual amount wounds. The concept “AIEzyme” would hopefully stimulate tremendous expansion kits application artificial enzymes.

Язык: Английский

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