Doping Engineering to Modulate Lattice and Electronic Structure for Enhanced Piezocatalytic Therapy and Ferroptosis

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(38)

Published: July 12, 2023

Piezocatalytic therapy, which generates reactive oxygen species (ROS) under mechanical force, has garnered extensive attention for its use in cancer therapy owing to deep tissue penetration depth and less O2 -dependence. However, the piezocatalytic therapeutic efficiency is limited poor piezoresponse, low separation of electron-hole pairs, complicated tumor microenvironment (TME). Herein, a biodegradable, porous Mn-doped ZnO (Mn-ZnO) nanocluster with enhanced piezoelectric effect constructed via doping engineering. Mn-doping not only induces lattice distortion increase polarization but also creates rich vacancies (OV ) suppressing recombination leading high-efficiency generation ROS ultrasound irradiation. Moreover, shows TME-responsive multienzyme-mimicking activity glutathione (GSH) depletion ability mixed valence Mn (II/III), further aggravating oxidative stress. Density functional theory calculations show that can improve performance enzyme Mn-ZnO due presence OV . Benefiting from boosting GSH ability, significantly accelerate accumulation lipid peroxide inactivate peroxidase 4 (GPX4) induce ferroptosis. The work may provide new guidance exploring novel sonosensitizers therapy.

Language: Английский

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Redox Homeostasis Disruptors Based on Metal‐Phenolic Network Nanoparticles for Chemo/Chemodynamic Synergistic Tumor Therapy through Activating Apoptosis and Cuproptosis

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(29)

Published: June 27, 2023

The combination of chemo/chemodynamic therapy is a promising strategy for improving antitumor efficacy. Herein, metal-phenolic network nanoparticles (NPs) self-assembled from copper ions and gallic acid (Cu-GA) are developed to evoke apoptosis cuproptosis synergistic therapy. Cu-GA NPs biodegraded in response the highly expressed glutathione (GSH) tumor cells, resulting simultaneous release Cu+ GA. intracellular GSH content dramatically reduced by released GA, rendering cells incapable scavenging reactive oxygen species (ROS) more susceptible cuproptosis. Meanwhile, ROS levels within significantly increased Fenton-like reaction , which disrupts redox homeostasis achieves apoptosis-related chemodynamic Moreover, massive accumulation further induces aggregation lipoylated dihydrolipoamide S-acetyltransferase downregulation iron-sulfur cluster protein, activating enhance efficacy NPs. experiments vivo demonstrate that exhibited excellent biosafety superior capacity, can efficiently inhibit growth tumors due activation specific hydrogen peroxide. These Cu-based provide potential build up efficient safe cancer

Language: Английский

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Architecture of Vanadium‐Based MXene Dysregulating Tumor Redox Homeostasis for Amplified Nanozyme Catalytic/Photothermal Therapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 21, 2023

Abstract Taking the significance of special microenvironment for tumor cell survival into account, disrupting redox homeostasis is highly prospective improving therapeutic efficacy. Herein, a multifunctional 2D vanadium‐based MXene nanoplatform, V 4 C 3 /atovaquone@bovine albumin (V /ATO@BSA, abbreviated as VAB) has been elaborately constructed ATO‐enhanced nanozyme catalytic/photothermal therapy. The within cells eventually disrupted, showing remarkable anti‐tumor effect. VAB nanoplatform with mixed vanadium valence states can induce cascade catalyzed reactions in microenvironment, generating plenty reactive oxygen species (ROS) effective glutathione consumption to amplify oxidative stress. Meanwhile, stable and strong photothermal effect under near‐infrared irradiation not only causes necrosis cells, but also improves its peroxidase‐like activity. In addition, release ATO effectively alleviate endogenous limit triphosadenine formation inhibit mitochondrial respiration. As result, expression heat shock proteins suppressed overcome thermoresistance production ROS be further promoted due injury. Moreover, presents high photoacoustic imaging performances. brief, provide therapy broadening biomedical applications MXene.

Language: Английский

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Capsaicin Enhanced the Efficacy of Photodynamic Therapy Against Osteosarcoma via a Pro‐Death Strategy by Inducing Ferroptosis and Alleviating Hypoxia

Small, Journal Year: 2024, Volume and Issue: 20(26)

Published: Jan. 14, 2024

Abstract Ferroptosis, a novel form of nonapoptotic cell death, can effectively enhance photodynamic therapy (PDT) performance by disrupting intracellular redox homeostasis and promoting apoptosis. However, the extremely hypoxic tumor microenvironment (TME) together with highly expressed hypoxia‐inducible factor‐1α (HIF‐1α) presents considerable challenge for clinical PDT against osteosarcoma (OS). Hence, an innovative nanoplatform that enhances antitumor inducing ferroptosis alleviating hypoxia is fabricated. Capsaicin (CAP) widely reported to specifically activate transient receptor potential vanilloid 1 (TRPV1) channel, trigger increase in Ca 2+ concentration, which closely linked ferroptosis, participate decreased oxygen consumption inhibiting HIF‐1α cells, potentiating efficiency. Thus, CAP photosensitizer IR780 are coencapsulated into biocompatible human serum albumin (HSA) construct (CI@HSA NPs) synergistic treatment under near‐infrared (NIR) irradiation. Furthermore, underlying signaling pathways combination investigated. CI@HSA NPs achieve real‐time dynamic distribution monitoring exhibit excellent efficacy superior biosafety vivo. Overall, this work highlights promising NIR imaging‐guided “pro‐death” strategy overcome limitations OS hypoxia, providing inspiration support future approaches.

Language: Английский

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Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Language: Английский

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Unlocking the potential of 1,4-naphthoquinones: A comprehensive review of their anticancer properties

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116249 - 116249

Published: Feb. 23, 2024

Cancer encompasses a group of pathologies with common characteristics, high incidence, and prevalence in all countries. Although there are treatments available for this disease, they not always effective or safe, often failing to achieve the desired results. This is why it necessary continue search new therapies. One strategies obtaining antitumor drugs use 1,4-naphthoquinone as scaffold synthetic natural products activity. review focuses on compiling studies related activity its derivatives over last 10 years. The work describes main naphthoquinones classifies based structural modifications made scaffold. Additionally, formation metal complexes using ligand considered. After thorough review, 197 compounds potent biological against cancer have been classified according their chemical structures mechanisms action described.

Language: Английский

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PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 266, P. 131359 - 131359

Published: April 4, 2024

Language: Английский

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Tumor Microenvironment Specific Regulation Ca‐Fe‐Nanospheres for Ferroptosis‐Promoted Domino Synergistic Therapy and Tumor Immune Response

Small, Journal Year: 2024, Volume and Issue: unknown

Published: May 27, 2024

Abstract Reactive oxygen species (ROS)‐mediated emerging treatments exhibit unique advantages in cancer therapy recent years. While the efficacy of ROS‐involved tumor is greatly restricted by complex microenvironment (TME). Herein, a dual‐metal CaO 2 @CDs‐Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power multiple cascade synergistic therapeutic strategy domino effect. In weak acidic TME, CCF will decompose, accompanied intracellular Ca 2+ upregulated abundant H O produced reverse antitherapeutic TME. Then exposed CF cores can act as both Fenton agent sonosensitizer generate excessive regulated for enhanced CDT/SDT. combination calcium overloading, augmented induced oxidative stress cause more severe mitochondrial damage cellular apoptosis. Furthermore, also reduce GPX4 expression enlarge lipid peroxidation, causing ferroptosis apoptosis parallel. These signals finally initiate damage‐associated molecular patterns activate immune realize excellent antitumor This outstanding ROS/calcium loading effect endows anticancer efficiently eliminate apoptosis/ferroptosis/ICD vitro vivo.

Language: Английский

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Tumor Microenvironment‐Activatable Metal‐Phenolic Nanoformulations for Ultrasound‐Boosted Ferroptosis through Triple Regulatory Pathways

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(44)

Published: July 16, 2024

Abstract Despite its effectiveness in exterminating tumor cells, ferroptosis is seriously hampered by the high expression of antioxidant glutathione (GSH) and inadequacy endogenous H 2 O tumors. Herein, metal‐phenolic nanoformulations (FNCP NFs) composed sonosensitizer Chlorin e6 (Ce6), phenolic GSH consumer naphthazarin, Fe 3+ , followed modification PEG2000, are strategically designed fabricated for ultrasound‐boosted cells through triple regulatory pathways. The carrier‐free FNCP NFs can rapidly dissociate under microenvironment response with assistance ultrasound, releasing 2+ Ce6, naphthazarin. Ce6 capable producing singlet oxygen ( 1 ) hydroxyl radicals · OH) ultrasound‐activated sonodynamic therapy Fenton reaction‐mediated chemodynamic (CDT), respectively, which not only induce apoptotic cell death but also lead to effective accumulation lipid peroxidation (LPO), resulting ferroptosis. Meanwhile, released naphthazarin self‐cycling valence alternations /Fe promote significant decrease intracellular contents, further inducing inactivation peroxidase 4 (GPX4) up‐regulation LPO levels, eventually realizing synergistically enhanced This facile feasible design versatile offers a new strategy effectively improving efficiency multimodal cancer therapies.

Language: Английский

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Fe/Mo‐Based Lipid Peroxidation Nanoamplifier Combined with Adenosine Immunometabolism Regulation to Augment Anti‐Breast Cancer Immunity

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Immunogenic cell death (ICD)-mediated immunization strategies have great potential against breast cancer. However, traditional neglect the increase in immunosuppressive metabolite, adenosine (ADO), during ICD, leading to insufficient therapeutic outcomes. In this study, it is found that A2A receptor (A2AR) significantly expressed cancer and positively associated with regulatory T (Treg) cells. Herein, a strategy combining Fe/Mo-based lipid peroxidation (LPO) nanoamplifiers A2AR blockade reported maximize ICD-mediated anti-tumor immunity. This LPO nanoamplifier causes explosion by Fe (II)-mediated Fenton reaction Mo(V)-mediated Russell mechanism. Subsequently, elicits ICD magnification of tumor cells inducing multiple regulated patterns ferroptosis, apoptosis, necroptosis. Additionally, antagonist (SCH58261), an immunometabolic checkpoint blocker, relieve ADO-related immunosuppression, amplify immunological effects, elicit immune memory responses. robust immunity observed primary, distant, pulmonary metastatic, recurrent tumors. study provides novel for optimizing immunotherapy highlights benefits enhance immunotherapy.

Language: Английский

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