Phototheranostic Metal-Phenolic Networks with Antiexosomal PD-L1 Enhanced Ferroptosis for Synergistic Immunotherapy

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(2), P. 787 - 797

Published: Jan. 5, 2022

Tumor-derived exosome can suppress dendritic cells (DCs) and T functions. Excessive secretion of exosomal programmed death-ligand 1 (PD-L1) results in therapeutic resistance to PD-1/PD-L1 immunotherapy clinical failure. Restored by antiexosomal PD-L1 tactic intensify ferroptosis tumor vice versa. Diminishing suppression establishing a nexus may rescue the discouraging antitumor immunity. Here, we engineered phototheranostic metal-phenolic networks (PFG MPNs) an assembly semiconductor polymers encapsulating inducer (Fe3+) inhibitor (GW4869). The PFG MPNs elicited superior near-infrared II fluorescence/photoacoustic imaging tracking performance for precise photothermal therapy (PTT). PTT-augmented immunogenic cell death relieved silencing on DC maturation. GW4869 mediated based inhibition revitalized enhanced ferroptosis. This novel synergy PTT with evoked potent immunity B16F10 tumors immunological memory against metastatic lymph nodes.

Language: Английский

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Recent applications of immunomodulatory biomaterials for disease immunotherapy

Exploration, Journal Year: 2022, Volume and Issue: 2(6)

Published: May 23, 2022

Immunotherapy is used to regulate systemic hyperactivation or hypoactivation treat various diseases. Biomaterial-based immunotherapy systems can improve therapeutic effects through targeted drug delivery, immunoengineering, etc. However, the immunomodulatory of biomaterials themselves cannot be neglected. In this review, we outline with functions discovered in recent years and their applications disease treatment. These inflammation, tumors, autoimmune diseases by regulating immune cell function, exerting enzyme-like activity, neutralizing cytokines, The prospects challenges biomaterial-based modulation are also discussed.

Language: Английский

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Carbon Quantum Dots-Based Nanozyme from Coffee Induces Cancer Cell Ferroptosis to Activate Antitumor Immunity

ACS Nano, Journal Year: 2022, Volume and Issue: 16(6), P. 9228 - 9239

Published: May 27, 2022

Carbon quantum dots (CQDs) offer huge potential due to their enzymatic properties as compared natural enzymes. Thus, discovery of CQDs-based nanozymes with low toxicity from resources, especially daily food, implies a promising direction for exploring treatment strategies human diseases. Here, we report biocompatible nanozyme prepared chlorogenic acid (ChA), major bioactive product coffee. We found that ChA CQDs exhibited obvious GSH oxidase-like activities and subsequently promoted cancer cell ferroptosis by perturbation GPX4-catalyzed lipid repair systems. In vivo, dramatically suppressed the tumor growth in HepG2-tumor-bearing mice negligible side toxicity. Particularly, hepatoma H22-bearing mice, recruited massive tumor-infiltrating immune cells including T cells, NK macrophages, thereby converting "cold" "hot" tumors activating systemic antitumor responses. Taken together, our study suggests product-derived coffee can serve biologically safe anticancer therapeutics may aid development nanotechnology-based immunotherapeutic.

Language: Английский

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A Hollow Amorphous Bimetal Organic Framework for Synergistic Cuproptosis/Ferroptosis/Apoptosis Anticancer Therapy via Disrupting Intracellular Redox Homeostasis and Copper/Iron Metabolisms

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(40)

Published: July 30, 2022

Abstract Cuproptosis is a very newly recognized regulated cell death modality that distinct from known mechanisms and shows enormous prospect in cancer treatment. However, its efficacy copper‐dependent restricted by strictly copper metabolism. Herein, novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) developed as an oxidative stress amplifier metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF fabricated Cu 2+ , 3,3′‐dithiobis(propionohydrazide) Fe 3+ via unsaturated coordination‐etching integration strategy, then doxorubicin loaded followed surface decoration with hyaluronan. obtained DOX@Fe/CuTH exhibits tumor microenvironment‐triggered catalytic therapeutic property, wherein it can amplify cellular simultaneously boosting H 2 O production depleting glutathione. Moreover, cause mitochondrial dysfunction downregulate the expressions of transporter ATP7A iron FPN 1, thereby leading to disorders high retentions cytoplasm •OH generation. overloaded lipoylated protein dihydrolipoamide S‐acetyltransferase aggregation lead cuproptosis. Collectively, both augmented induce potent ferroptosis, which synergizes cuproptosis DOX‐mediated apoptosis efficiently suppress growth. This bimetallic nanoplatform provides new paradigm boost cuproptosis‐related therapies.

Language: Английский

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Microenvironment-driven sequential ferroptosis, photodynamic therapy, and chemotherapy for targeted breast cancer therapy by a cancer-cell-membrane-coated nanoscale metal-organic framework

Biomaterials, Journal Year: 2022, Volume and Issue: 283, P. 121449 - 121449

Published: March 1, 2022

Language: Английский

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Metallodrugs in cancer nanomedicine

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(7), P. 2544 - 2582

Published: Jan. 1, 2022

Metal complexes are extensively used for cancer therapy. The multiple variables available tuning (metal, ligand, and metal-ligand interaction) offer unique opportunities drug design, have led to a vast portfolio of metallodrugs that can display higher diversity functions mechanisms action with respect pure organic structures. Clinically approved metallodrugs, such as cisplatin, carboplatin oxaliplatin, treat many types play prominent roles in combination regimens, including immunotherapy. However, generally suffer from poor pharmacokinetics, low levels target site accumulation, metal-mediated off-target reactivity development resistance, which all limit their efficacy clinical translation. Nanomedicine has arisen powerful tool help overcome these shortcomings. Several nanoformulations already significantly improved the reduced toxicity (chemo-)therapeutic drugs, some promising metallodrug-containing nanomedicines currently trials. In this critical review, we analyse challenges assess advantages limitations metallodrug delivery, both nanocarrier metal-nano interaction perspective. We describe latest most relevant nanomedicine formulations developed metal complexes, discuss how rational coordination chemistry technology assist promoting translation metallodrugs.

Language: Английский

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A “Closed‐Loop” Therapeutic Strategy Based on Mutually Reinforced Ferroptosis and Immunotherapy

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(13)

Published: Feb. 1, 2022

Abstract The immunosuppression and immune escape of current immunotherapy result in low efficacy, ferroptosis is greatly restricted by the reactive oxygen species (ROS) production efficiency. Here, for first time a “closed‐loop” therapy based on photothermal enhancement stimulated each other multifunctional nanoplatform reported. This platform composed copper silicate iron mesoporous hollow nanospheres, followed situ growth Au nanoparticles loading an adjuvant resiquimod R848. laser irradiation‐mediated heat introduction ions significantly enhance ROS generation, leading to simultaneous depletion glutathione peroxidase 4 (GPX4) (GSH). onset tumor cells thus enhanced response with immunogenic cell death (ICD) triggered, promoting dendritic (DCs) maturation T infiltration. Interferon γ (IFN‐γ) released from CD8 + downregulates expression SLC7A11 GPX4, which turn enhances expression, constituting “closed‐Loop” therapy. Importantly, this system effective both killing primary inhibiting metastasis. proposed therapeutic strategy may provide guidance design future antitumor nanoplatforms.

Language: Английский

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Bioactive inorganic nanomaterials for cancer theranostics

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(6), P. 2031 - 2081

Published: Jan. 1, 2023

Bioactive materials are a special class of biomaterials that can react in vivo to induce biological response or regulate functions, thus achieving better curative effect than traditional inert biomaterials. For cancer theranostics, compared with organic polymer nanomaterials, inorganic nanomaterials possess unique physical and chemical properties, have stronger mechanical stability on the basis maintaining certain bioactivity, easy be compounded various carriers (polymer carriers, etc.), so as achieve specific antitumor efficacy. After entering nanoscale, due nano-size effect, high surface area nanostructures, exhibit effects, which significantly influence interaction organisms. Therefore, research applications bioactive theranostics attracted wide attention. In this review, we mainly summarize recent progress also introduce definition, synthesis modification strategies nanomaterials. Thereafter, tumor imaging therapy, including microenvironment (TME) regulation, catalytic gas regulatory cell death immunotherapy, discussed. Finally, biosafety challenges mentioned, their future development opportunities prospected. This review highlights bioapplication

Language: Английский

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Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(17)

Published: May 4, 2022

Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis a newly discovered method programmed cell death opens new direction for GBM treatment. However, poor blood-brain barrier (BBB) penetration, reduced tumor targeting ability, potential compensatory mechanisms hinder effectiveness ferroptosis agents during Here, novel composite therapeutic platform combining magnetic features drug delivery properties nanoparticles with BBB penetration abilities siRNA encapsulation engineered exosomes therapy presented. This can be enriched in brain under local localization angiopep-2 peptide-modified trigger transcytosis, allowing particles to cross target cells by recognizing LRP-1 receptor. Synergistic achieved combined triple actions disintegration dihydroorotate dehydrogenase glutathione peroxidase 4 defense axis Fe

Language: Английский

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Ferroptosis‐Enhanced Cancer Immunity by a Ferrocene‐Appended Iridium(III) Diphosphine Complex

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(16)

Published: Dec. 29, 2021

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report IrIII complex (Ir1) containing ferrocene-modified diphosphine ligand that localizes lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4, result ferroptosis. RNA sequencing analysis shows significantly affect pathways related to ferroptosis cancer immunity. Accordingly, immunogenic cells suppress tumor growth vitro, regulate T activity immune microenvironments vivo. In conclusion, show small molecules with capabilities for effective immunotherapy.

Language: Английский

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