A Multichannel Metabolic Pathway Interference Strategy for Complete Energy Depletion‐Mediated Cancer Therapy

Advanced Functional Materials, Год журнала: 2024, Номер 34(19)

Опубликована: Янв. 18, 2024

Abstract Hydrogen sulfide (H 2 S) is being progressively integrated as an emerging inhibitor of the electron transport chain in energy interference‐based tumor therapy. However, metabolic reprogramming cancer cells causes both oxidative phosphorylation (OXPHOS) and glycolysis to occur simultaneously, which contributes ineffective therapeutic effect blocking a single pathway. To achieve complete suppression production, inorganic H S donor ZnS@ZIF‐8@CaP nanoparticle (ZSZC NP) carrying Ca Zn constructed for achieving simultaneous interference OXPHOS glycolysis. The core–shell ZSZC nanoparticles can break down microenvironment. This leads sustained release calcium overload disrupt normal functioning mitochondria by inhibiting expression cytochrome c causing damage mitochondrial membrane potential. Meanwhile, presence 2+ hinders typical process impeding lactate dehydrogenase glyceraldehyde‐3‐phosphate dehydrogenase. synchronous hampers supply cells. Additionally, expedite necrosis vivo inducing cellular acidification calcification. Therefore, this energy‐blocking strategy will completely deplete reserves provide new insights exploring bioenergetic inhibition treatment approach.

Язык: 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, Год журнала: 2024, Номер 18(20), С. 12830 - 12844

Опубликована: Май 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

Язык: Английский

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Trisulfide Bond‐Mediated Molecular Phototheranostic Platform for “Activatable” NIR‐II Imaging‐Guided Enhanced Gas/Chemo‐Hypothermal Photothermal Therapy

Advanced Science, Год журнала: 2023, Номер 10(36)

Опубликована: Ноя. 20, 2023

Abstract Tumor microenvironment (TME)‐triggered phototheranostic platform offers a feasible strategy to improve cancer diagnosis accuracy and minimize treatment side effects. Developing stable biocompatible molecular for TME‐activated second near‐infrared (NIR‐II) fluorescence imaging‐guided multimodal cascade therapy is promising creating desirable anticancer agents. Herein, new NIR‐II activatable (IR‐FEP‐RGD‐S‐S‐S‐Fc) presented actively targeted tumor imaging hydrogen sulfide (H 2 S) gas‐enhanced chemodynamic‐hypothermal photothermal combined (CDT/HPTT). It revealed the first time that coupling distance between IR‐FE ferrocene proportional photoinduced electron transfer (PET), aqueous environment favorable PET generation. The part of Cyclic‐RGDfK (cRGDfk) peptides can target benefit endocytosis nanoparticles. high‐concentration glutathione (GSH) in TME will separate molecule by GSH‐sensitive trisulfide bond, realizing light‐up trimodal synergistic CDT/HPTT/gas (GT). In addition, accumulation hydroxyl radicals (•OH) down‐regulation peroxidase 4 (GPX4) produce excessive harmful lipid hydroperoxides, ultimately leading ferroptosis.

Язык: Английский

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Multifunctional 3D-printed scaffolds eradiate orthotopic osteosarcoma and promote osteogenesis via microwave thermo-chemotherapy combined with immunotherapy

Biomaterials, Год журнала: 2023, Номер 301, С. 122236 - 122236

Опубликована: Июль 18, 2023

Язык: Английский

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A metal-organic framework (MOF) built on surface-modified Cu nanoparticles eliminates tumors via multiple cascading synergistic therapeutic effects

Journal of Colloid and Interface Science, Год журнала: 2024, Номер 662, С. 298 - 312

Опубликована: Фев. 9, 2024

Язык: Английский

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H₂S‐Mediated Gas Therapy and HSP90 Downregulation Synergically Enhance Tumor Microwave Thermal Therapy

Advanced Functional Materials, Год журнала: 2024, Номер 34(21)

Опубликована: Янв. 23, 2024

Abstract Microwave thermal therapy (MWTT) is a novel clinical treatment of tumors via inducing effect and anti‐tumor immune response, exhibiting advantages deep penetration, minimal invasion, high heat conversion efficiency. However, effective ablation difficult to cover the entire tumor area, heat‐shock protein 90 (HSP90) often upregulated after generate tolerance sublethal weaken induced antitumor effect, resulting in rate recurrence metastasis. Herein, multifunctional nanoregulator metal phenolic network‐coated ZnS (ZnS@Ga‐tannic acid, ZGT) proposed release H 2 S for synergically enhancing MWTT. Under costimulation MW radiation acidic microenvironment, ZGT can improve effects promote damage induce apoptosis. The released also inhibit production ATP then downregulate expression HSP90, strengthening activated systemic response ablation. This provides new way achieving compensation strategy gas HSP90 positively regulate introduces direction reducing risk metastasis therapy.

Язык: Английский

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pH-Responsive nanoplatform synergistic gas/photothermal therapy to eliminate biofilms in poly(l-lactic acid) scaffolds

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(5), С. 1379 - 1392

Опубликована: Янв. 1, 2024

The constructed ZnS–Ti 3 C 2 /PLLA scaffolds were able to release H S gas disrupt biofilm and further remove bacteria through photothermal. In addition, the Zn 2+ released from composite could promote osteogenic differentiation of BMSCs.

Язык: Английский

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Nanomaterial-based regulation of redox metabolism for enhancing cancer therapy

Chemical Society Reviews, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

This review provides a comprehensive summary of the dysregulation redox metabolism in cancer cells and advantages latest advances nanomaterial-assisted metabolic regulation therapy.

Язык: Английский

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Recent Advances on NIR‐II Light‐Enhanced Chemodynamic Therapy

Advanced Healthcare Materials, Год журнала: 2023, Номер 13(10)

Опубликована: Ноя. 21, 2023

Abstract Chemodynamic therapy (CDT) is a particular oncological therapeutic strategy by generates the highly toxic hydroxyl radical (•OH) from dismutation of endogenous hydrogen peroxide (H 2 O ) via Fenton or Fenton‐like reactions. However, single CDT therapies have been limited unsatisfactory efficacy. Enhanced chemodynamic (ECDT) triggered near‐infrared (NIR) novel modality based on light energy to improve efficiency penetration and imaging capability visible (400–650 nm) traditional NIR‐I region (650–900 light‐amplified restrict prospects for its clinical application. Combined with high penetration/high precision characteristics second (NIR‐II,) nanoplatform, it expected kill deep tumors efficiently while treatment process in real‐time, more notably, NIR‐II radiation wavelengths above 1000 nm can minimize irradiation damage normal tissues. Such ECDT nanoplatforms greatly improved effectiveness demonstrated extraordinary potential applications. Accordingly, various strategies explored past years CDT. In this review, mechanisms used performance NIR‐II‐enhanced are outlined.

Язык: Английский

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Multi‐Enzyme Nanoparticles as Efficient Pyroptosis and Immunogenic Cell Death Inducers for Cancer Immunotherapy

Advanced Science, Год журнала: 2024, Номер 11(44)

Опубликована: Окт. 9, 2024

Abstract Immunotherapy represents a widely employed modality in clinical oncology, leveraging the activation of human immune system to target and eradicate cancer cells tumor tissues via endogenous mechanisms. However, its efficacy remains constrained by inadequate responses within “cold” microenvironment (TME). In this study, multifunctional nanoscale pyroptosis inducer with cascade enzymatic activity (IMZF), comprising superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione oxidase (GSHO x ), is dissociated acidic glutathione‐rich TME. The vigorous not only generates oxygen (O 2 ) alleviate hypoxia promote M2 M1 macrophage polarization but also yields reactive species (ROS) depletes (GSH) Functioning as an immunogenic cell death (ICD) activator inducer, IMZF synergistically triggers dendritic maturation inflammatory lymphocyte infiltration ICD‐associated pyroptosis, thereby reversing suppression TMEs. Consequently, it exerts inhibitory effects on both primary distal tumors. This platform‐based offers intelligent strategy for effectively overcoming tumors, providing promising avenue advanced immunotherapeutic interventions.

Язык: Английский

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