Near-Infrared-II-Activatable Self-Assembled Manganese Porphyrin-Gold Heterostructures for Photoacoustic Imaging-Guided Sonodynamic-Augmented Photothermal/Photodynamic Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 18(1), P. 713 - 727

Published: Dec. 20, 2023

Porphyrins and their derivatives are widely used as photosensitizers sonosensitizers in tumor treatment. Nevertheless, poor water solubility low chemical stability reduce singlet oxygen (1O2) yield and, consequently, photodynamic therapy (PDT) sonodynamic (SDT) efficiency. Although strategies for porphyrin molecule assembly have been developed to augment 1O2 generation, there is scope further improving PDT SDT efficiencies. Herein, we synthesized ordered manganese (SM) nanoparticles with well-defined self-assembled metalloporphyrin networks that enabled efficient energy transfer enhanced photocatalytic sonocatalytic activity production. Subsequently, Au were grown situ on the SM surface by anchoring terminal alkynyl of form plasmonic SMA heterostructures, which showed excellent near-infrared-II (NIR-II) region absorption photothermal properties, facilitated electron–hole pair separation transfer. With modification hyaluronic acid (HA), SMAH heterostructure nanocomposites exhibited good actively targeted cancer cells. Under NIR-II light ultrasound (US) irradiation, generates hyperthermia, a large amount 1O2, inducing cell damage. Both vitro vivo studies confirmed effectively suppressed growth decreasing GSH levels SDT-augmented PDT/PTT. Moreover, utilizing strong window, can achieve photoacoustic imaging-guided combined This work provides paradigm enhancing metalloporphyrins improve synergistic therapeutic effect SDT/PDT/PTT.

Language: Английский

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Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response

ACS Nano, Journal Year: 2024, Volume and Issue: 18(15), P. 10495 - 10508

Published: April 1, 2024

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via Jahn–Teller effect induced by introduction of Cu2+, synthesized regulated intricate microenvironment (TME) depleting endogenous glutathione (GSH) amplify oxidative stress further enhanced performance. Furthermore, cuproptosis evoked intracellular overload Cu2+ amplified SDT, leading irreversible proteotoxicity. In vitro results showed that such synergetic triggered immunogenic cell death (ICD) promoted maturation dendritic cells (DCs). as-synthesized NS-mediated thoroughly eradicated vivo solid tumors simultaneously elicited antitumor immunity suppress lung liver metastasis. Overall, this work established a nanoplatform with satisfactory immunity.

Language: Английский

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Gas-Amplified Metalloimmunotherapy with Dual Activation of Pyroptosis and the STING Pathway for Remodeling the Immunosuppressive Cervical Cancer Microenvironment

ACS Nano, Journal Year: 2024, Volume and Issue: 18(20), P. 12830 - 12844

Published: May 6, 2024

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance antitumor immune response through gas-amplified metalloimmunotherapy with dual activation pyroptosis and STING pathway. bioactive MCSP exhibited ability rapidly release Ca2+, Mn2+, H2S in tumor microenvironment. disrupted buffer system cells by interfering oxidative phosphorylation pathway, leading overload-triggered pyroptosis. On other hand, H2S-mediated mitochondrial dysfunction further promoted DNA (mtDNA), enhancing effect Mn2+ on cGAS-STING signaling axis thereby activating immunosuppressed dendritic cells. released acted as an important synergist between Ca2+ modulating mechanisms bridge innate adaptive responses. combination NPs PD-1 immunotherapy achieved synergistic effects inhibited growth. This study reveals potential collaboration gas therapy provides idea for design nanoimmunomodulators rational regulation

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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Optimization of Schottky barrier height and LSPR effect by dual defect induced work function changes for efficient solar-driven hydrogen production

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 490, P. 151822 - 151822

Published: May 1, 2024

Language: Английский

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Defect‐Repaired g‐C₃N₄ Nanosheets: Elevating the Efficacy of Sonodynamic Cancer Therapy Through Enhanced Charge Carrier Migration

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: Feb. 7, 2024

Sonodynamic therapy (SDT) has garnered growing interest owing to its high tissue penetration depth and minimal side effects. However, the lack of efficient sonosensitizers remains primary limiting factor for clinical application this treatment method. Here, defect-repaired graphene phase carbon nitride (g-C

Language: Английский

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Exploration of Ultrasound‐Sensitive Biomaterials in Cancer Theranostics

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(21)

Published: Jan. 6, 2024

Abstract Cancer is a serious health problem to be solved. With the development of biomaterials, enhanced diagnostic and controllable therapeutic strategies for cancer have emerged, revealing encouraging results with promising future. Due its outstanding tissue penetration controllability, along series bioeffects on tissues, ultrasound (US), as common medical technology, has been regarded an effective tool against cancer, use promoted exploration US‐sensitive biomaterials. In this review, US are first introduced then main biomaterials (containing cavitation nuclei, sonosensitizers, US‐responsive macromolecular systems) used treat followed by summary several applications based from diagnosis therapy. Finally, emerging challenges in field that need overcome highlighted. This review reports progress providing new possibilities theranostics thus benefiting patients.

Language: Английский

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Employing Piezoelectric Mg²⁺‐Doped Hydroxyapatite to Target Death Receptor‐Mediated Necroptosis: A Strategy for Amplifying Immune Activation

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 22, 2024

Abstract Although immunogenic cell death (ICD) inducers evidently enhance the effectiveness of immunotherapy, their potential is increasingly restricted by development apoptosis resistance in tumor cells, poor immunogenicity, and low T‐cell immune responsiveness. In this study, for first time, piezoelectrically catalyzed Mg 2+ ‐doped hydroxyapatite (Mg‐HAP) nanoparticles, which are coated with a mesoporous silica layer loaded ONC201 as an agonist to specifically target receptor DR5 on ultimately developing Mg‐HAP@MS/ONC201 nanoparticle (MHMO NP) system, engineered. Owing its excellent piezoelectric properties, MHMO facilitates release significant amount reactive oxygen species Ca within effectively promoting upregulation expression inducing necroptosis overcome resistance. Concurrently, released microenvironment promotes CD8 + T activation response antitumor reaction induced ICD. Using RNA‐seq analysis, it elucidated that can activate NF‐κB pathway under catalysis, thus M1‐type macrophage polarization. summary, dual‐targeting therapy system targets both cells catalysis designed. This holds substantial advancements immunotherapy.

Language: Английский

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Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Gasdermin (GSDM)-mediated pyroptosis involves the induction of mitochondrial damage and subsequent release DNA (mtDNA), which is anticipated to activate cGAS-STING pathway, thereby augmenting antitumor immune response. However, challenges lie in effectively triggering cancer cells subsequently enhancing activation with specificity. Herein, we developed intelligent self-cascaded pyroptosis-STING initiators cobalt fluoride (CoF2) nanocatalysts for catalytic metalloimmunotherapy. CoF2 a semiconductor structure enzyme-like activity generated substantial amount reactive oxygen species (ROS) under stimulation by endogenous H2O2 exogenous ultrasound. Importantly, discovered that Co-based nanomaterials themselves induce cells. Therefore, initially acted as inducers, caspase-1/GSDMD-dependent via Co2+ ROS, leading mtDNA release. Subsequently, were further utilized STING agonists specifically capable detecting pathway. These cascade events triggered robust response, modulating immunosuppressive tumor microenvironment into an immune-supportive state, providing favorable support therapy. This innovative strategy not only significantly impeded growth primary but also elicited response augment efficacy checkpoint inhibitors preventing distant progression. Overall, this study proposed self-cascade activating amplifying pathway specificity mediated pyroptosis, representing valuable avenue future

Language: Английский

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Amplifying “eat me signal” by immunogenic cell death for potentiating cancer immunotherapy

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 94 - 114

Published: Aug. 7, 2023

Immunogenic cell death (ICD) is a unique mode of death, which can release immunogenic damage-associated molecular patterns (DAMPs) and tumor-associated antigens to trigger long-term protective antitumor immune responses. Thus, amplifying "eat me signal" during tumor ICD cascade critical for cancer immunotherapy. Some therapies (radiotherapy, photodynamic therapy (PDT), photothermal (PTT), etc.) inducers (chemotherapeutic agents, have enabled initiate and/or facilitate activate Recently, nanostructure-based drug delivery systems been synthesized inducing through combining treatment chemotherapeutic photosensitizers PDT, transformation agents PTT, radiosensitizers radiotherapy, etc., loaded at an appropriate dosage in the designated place time, contributing higher efficiency lower toxicity. Also, immunotherapeutic combination with produce synergetic effects, thus potentiating Overall, our review outlines emerging inducers, nanostructure loading diverse evoke chemoradiotherapy, PTT or agents. Moreover, we discuss prospects challenges harnessing induction-based immunotherapy, highlight significance multidisciplinary interprofessional collaboration promote optimal translation this strategy.

Language: Английский

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