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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Supramolecular Coordination Complexes for Synergistic Cancer Therapy

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(8), P. 1174 - 1187

Published: April 1, 2024

ConspectusSupramolecular coordination complexes (SCCs) are predictable and size-tunable supramolecular self-assemblies constructed through directional bonds between readily available organic ligands metallic receptors. Based on planar 3D structures, SCCs can be mainly divided into two categories: metallacycles (e.g., rhomboidal, triangular, rectangular, hexagonal) metallacages tetrahedral, hexahedral, dodecahedral). The enable the efficient formation of with well-defined architectures geometries. exhibit several advantages, including good directionality, strong interaction force, tunable modularity, solution processability, making them highly attractive for biomedical applications, especially in cellular imaging cancer therapy. Compared their molecular precursors, demonstrate enhanced uptake a strengthened tumor accumulation effect, owing to inherently charged structures. These properties chemotherapeutic potential inherent platinum have promoted widespread application antitumor Furthermore, defined structures SCCs, achieved via design modification assembly elements introduction different functional groups, combat malignant tumors multipronged treatment modalities. Because development cancer-treatment methodologies integrated clinics has evolved from single-modality chemotherapy synergistic multimodal therapy, therapy is crucial. While some pioneering reviews explored bioapplications often categorized by specific function or focusing metal ligand types, comprehensive exploration multifunctionality critical gap current literature.In this Account, we focus platinum-based applications other metals, such as Pd-, Rh-, Ru-, Ir-based been Therrien Casini et al., garnered significant interest, unique advantages which enhance efficacy, considered prominent candidates therapies desirable properties, potent activity, exceptionally low systemic toxicity, active tumor-targeting ability, uptake. diverse diagnostic therapeutic modalities chemotherapy, photothermal photodynamic therapy) single platform based Consequently, herein, summarize our recent research particular emphasis cooperative interplay methods. In Conclusions section, present key advancements basis findings propose future directions that may significantly impact field.

Language: Английский

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Supramolecular and molecular capsules, cages and containers

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(21), P. 10380 - 10408

Published: Jan. 1, 2024

Stemming from early seminal notions of molecular recognition and encapsulation, three-dimensional, cavity-containing capsular compounds assemblies have attracted intense interest due to the ability modulate chemical physical properties species encapsulated within these confined spaces compared bulk environments. With such a diverse range covalent motifs non-covalent (supramolecular) interactions available assemble building blocks, an incredibly wide-range capsular-type architectures been developed. Furthermore, synthetic tunability internal environments gives chemists opportunity engineer systems for uses in sensing, sequestration, catalysis transport molecules, just name few. In this tutorial review, overview is provided into design principles, synthesis, characterisation, structural facets coordination cages, porous organic supramolecular capsules, foldamers mechanically interlocked molecules. Using recent examples, advantages limitations each system are explored, highlighting their application various tasks functions.

Language: Английский

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Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: April 2, 2024

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high affinity can resist unwanted dissociation induced by dilution effect interferents within physiological environments. the other stimulus-responsive guest is essential precisely activating its function. In this context, we expanded hydrophobic cavity surface hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced aqueous to 10

Language: Английский

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Supramolecular Polymers for Drug Delivery

Chemistry - A European Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Supramolecular polymers are constructed through highly reversible and directionally specific non‐covalent interactions between monomer units. This unique feature enables supramolecular to undergo controlled structural reconfiguration functional transformation in response external stimuli, imparting them with high environmental responsiveness self‐healing properties. In particular, exhibit several advantages compared conventional polymers, such as inherent degradability, the ease of preparation incorporation units, smart various biological stimuli. These characters make promising candidates for intelligent drug delivery systems complex environments. this review, we comprehensively summarize latest developments representative achievements fields, focusing primarily on design synthesis, properties functionalities, practical applications small molecule delivery, gene therapy, protein delivery. Finally, highlight future research directions, multifunctionality, adaptability, personalized therapy. We focus recent studies that address key challenges field, providing rational polymer design, important properties, functionality, understanding strategies. expected advance new platforms systems, offering innovative solutions treatment diseases.

Language: Английский

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Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(23)

Published: April 2, 2024

Abstract The development of artificial receptors that combine ultrahigh‐affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high affinity can resist unwanted dissociation induced by dilution effect interferents within physiological environments. the other stimulus‐responsive guest is essential precisely activating its function. In this context, we expanded hydrophobic cavity surface hypoxia‐responsive azocalix[4]arene, affording Naph‐SAC4A. This modification significantly enhanced aqueous to 10 13 M −1 , akin naturally occurring strongest recognition pair, biotin/(strept−)avidin. Consequently, Naph‐SAC4A emerges as first receptor simultaneously integrate ultrahigh actively release. markedly not only improved Naph‐SAC4A′s sensitivity detecting rocuronium bromide serum, but also refined precision doxorubicin delivery at cellular level, demonstrating immense potential diverse practical

Language: Английский

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Integrating Photothermal, Photodynamic, and Chemodynamic Therapies: The Innovative Design Based on Copper Sulfide Nanoparticles for Enhanced Tumor Therapy

ACS Applied Bio Materials, Journal Year: 2024, Volume and Issue: 8(1), P. 676 - 687

Published: Dec. 30, 2024

A multifunctional nanoplatform integrating multiple therapeutic functions may be an effective strategy to realize satisfactory efficacy in the treatment of tumors. However, there is still a certain challenge agents into single formulation using simple method due variations their properties. In this work, CuS-ICG@PDA-FA nanoparticles (CIPF NPs) with excellent ability produce reactive oxygen species and photothermal conversion performance are fabricated by gentle method. Hollow mesoporous copper sulfide (HMCuS not only have loading but also can cause highly efficient Fenton-like reaction for chemodynamic therapy (CDT). The loaded photosensitizer indocyanine green (ICG) imparts photodynamic properties NPs, which turn enhances stability ICG. polydopamine (PDA) coating improves biocompatibility NPs creates conditions surface modification folic acid. FA-coated show precise targeting tumor cells. results cellular uptake assay demonstrate that CIPF enter cells through endocytic pathway. Lysosome colocalization escape experiments prove possess good lysosomal under irradiation NIR. Both vitro vivo antitumor studies reveal photothermal/photodynamic/chemodynamic therapy. construction high-performance offers valuable insights design sulfide-based combined cancer theranostics.

Language: Английский

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