A strategy of “adding fuel to the flames” enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy

Biomaterials, Journal Year: 2024, Volume and Issue: 311, P. 122701 - 122701

Published: July 6, 2024

Language: Английский

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Self‐Sustained Biophotocatalytic Nano‐Organelle Reactors with Programmable DNA Switches for Combating Tumor Metastasis

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

Published: Jan. 10, 2025

Abstract Metastasis, the leading cause of mortality in cancer patients, presents challenges for conventional photodynamic therapy (PDT) due to its reliance on localized light and oxygen application tumors. To overcome these limitations, a self‐sustained organelle‐mimicking nanoreactor is developed here with programmable DNA switches that enables bio‐chem‐photocatalytic cascade‐driven starvation‐photodynamic synergistic against tumor metastasis. Emulating compartmentalization positional assembly strategies found living cells, this nano‐organelle reactor allows quantitative co‐compartmentalization multiple functional modules designed self‐illuminating chemiexcited PDT system. Within space‐confined nanoreactor, biofuel glucose converted hydrogen peroxide (H 2 O ) which enhances luminol‐based chemiluminescence (CL), consequently driving generation photochemical singlet ( 1 via resonance energy transfer. Meanwhile, hemoglobin functions as synchronized supplier both oxidation PDT, while also exhibiting peroxidase‐like activity produce hydroxyl radicals (·OH). Crucially, keeps switching off normal tissues, on‐demand activation tumors through toehold‐mediated strand displacement. These findings demonstrate self‐sufficient precise striking tumors, promising paradigm managing highly metastatic cancers.

Language: Английский

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Dual‐Release Free Iron and Breakdown of Ferroptosis Defenses to Achieve Ferroptosis Cascade Storms for Potent Antitumor Therapy

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

Published: Jan. 19, 2025

Abstract Ferroptosis is a newly identified type of regulated cell death characterized by iron‐dependent lipid peroxidation. Among the main ferroptosis‐suppressing systems, dihydroorotate dehydrogenase (DHODH)‐ ubiquinone axis closely related to mitochondria and energy metabolism, implying that protects cells from oxidative stress damage via maintenance redox homeostasis. However, ferroptosis initiation requires suitable environment breakthrough in homeostatic limitations systems. Hence, nanoparticles are rationally engineered achieve efficient induction releasing dual‐release free iron disrupting Atovaquone (ATO)‐loaded hollow mesoporous etching zeolitic imidazolate framework‐67 double‐coated oxide/calcium phosphate (Fe 3 O 4 /CaP) conjugated with polyethylene glycol. The external Fe /CaP structure enhances efficiency multiple reactive oxygen species (ROS) generation promoting stress. Still, it achieves increase content unstable pools for igniting ROS storm peroxidation spark. release ATO not only affects metabolism mitochondrial respiratory chain binding complex III but also downregulates DHODH restrict ubiquinol system disrupt Therefore, design this composite nanomedicine provides an approach inducing theoretical basis clinical anti‐tumor trials.

Language: Английский

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MXBOTs: Biodegradable Ti₃C₂ MXene-Based Microrobots for Targeted Delivery and Synergistic Chemo-Photothermal Therapy

ACS Materials Letters, Journal Year: 2024, Volume and Issue: 6(5), P. 1801 - 1810

Published: April 3, 2024

Functions such as biocompatibility, degradability, therapeutics, and imaging are critical for use of microrobots in clinical scenarios; however, incorporation these functions into a single microrobotic entity is still challenging. Herein, we report multifunctional Ti3C2 MXene-based magnetically actuated (MXBOTs), which prepared by sequentially electrostatic coating nanosheets Fe3O4 nanoparticles on the surface biodegradable gelatin methacryloyl (GelMA)-based helical microstructures. These MXBOTs can move along predefined paths under rotating magnetic field. The provides with an advantageous photothermal effect photoacoustic (PA) capability. Additionally, be loaded fluorescent molecules, enabling fluorescence imaging. After loading chemotherapeutic drug DOX, MXBOTs@DOX were able to accelerate release DOX stimulation temperature acidic pH. This work presents viable approach developing functional targeted delivery synergistic chemo-photothermal therapy.

Language: Английский

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Prussian Blue‐Derived Nanocomposite Synergized with Calcium Overload for Three‐Mode ROS Outbreak Generation to Enhance Oncotherapy

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(22)

Published: June 11, 2024

Abstract Calcium overload can lead to tumor cell death. However, because of the powerful calcium channel excretory system within cells, simplistic overloads do not allow for an effective antitumor therapy. Hence, nanoparticles are created with polyethylene glycol (PEG) donor‐modified phosphate (CaP)‐coated, manganese‐doped hollow mesopores Prussian blue (MMPB) encapsulating glucose oxidase (GOx), called GOx@MMPB@CaP‐PEG (GMCP). GMCP a three‐mode enhancement intratumor reactive oxygen species (ROS) levels is designed increase efficiency intracellular in cells enhance its anticancer efficacy. The released exogenous Ca 2+ and production cytotoxic ROS resulting from perfect circulation outbreak generation that Fenton/Fenton‐like reaction consumption glutathione Fe /Fe 3+ Mn /Mn circle, amelioration hypoxia MMPB‐guided GOx‐mediated starvation Photothermal efficacy‐induced heat owing MMPB accelerates above reactions. Furthermore, abundant contribute damage mitochondria, channels efflux inhibited, overload. further increases promotes apoptosis achieve excellent

Language: Английский

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Wireless Powered Microwave-Light Conversion Platform with Dual-Stimulus Nanoresponder Coating for Deep-Seated Photodynamic Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(26), P. 17086 - 17099

Published: June 19, 2024

Traditional external field-assisted therapies, e.g., microwave (MW) therapy and phototherapy, cannot effectively minimally damage eliminate deep-seated infection, owing to the poor penetrability of light low reactive oxygen species (ROS) stimulation capability MW. Herein, an implantable wireless-powered therapeutic platform (CNT-FeTHQ-TS), in which MW can be converted into internal via light-emitting chips, is designed eradicate tissue infections by MW-induced photodynamic therapy. In application, CNT-FeTHQ-TS implanted at lesions, chip emits under irradiation. Subsequently, CNT-FeTHQ coating respond both simultaneously generate ROS MW-hyperthermia for rapid precise sterilization focus. Importantly, also improves performance introducing vacancies FeTHQ facilitate photoexcitation process changing spin state electrons inhibit complexation photogenerated electron-hole pairs, were confirmed simulation calculations situ MW-irradiated photoluminescence experiments. vivo, cure mice with Staphylococcus aureus infection dorsal subcutaneous tissue. This work overcomes key clinical limitations safe energy transmission conversion treating infections.

Language: Английский

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MOF-Derived Oxygen-Deficient Titania-Mediated Photodynamic/Photothermal-Enhanced Immunotherapy for Tumor Treatment

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(27), P. 34591 - 34606

Published: June 25, 2024

Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy been largely limited by weak immune response and an immunosuppressive tumor microenvironment. Herein, we report metal–organic framework (MOF)-derived titanium oxide nanoparticle (MCTx NP) booster that can greatly improve the immunotherapy inducing "immunogenic cell death" (ICD) remodeling The NPs, inheriting characteristic structure of MIL-125 enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency reactive species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, NPs release O2 reduce glutathione (GSH) in environment, showcasing their potential to reverse In vitro/vivo results MCTx directly kill cells effectively eliminate primary tumors exerting dual photodynamic/photothermal therapy under single NIR irritation. At same time, augment PD-L1 blockade potently ICDs reversing microenvironment, including promoting dendritic (DC) maturation, decreasing regulatory T (Tregs)' infiltration, increasing cytotoxic lymphocytes (CTLs) helper (Ths), resulting effective distant suppression. This work highlights NP-mediated photodynamic- photothermal-enhanced strategy treatment.

Language: Английский

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Synchronous Interference of Dual Metabolic Pathways Mediated by H₂S Gas/GOx for Augmenting Tumor Microwave Thermal Therapy

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Sublethal tumor cells have an urgent need for energy, making it common them to switch metabolic phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) compensatory energy supply; thus, the synchronous interference of dual pathways limiting level is essential in inhibiting sublethal growth. Herein, a multifunctional nanoplatform Co-MOF-loaded anethole trithione (ADT) myristyl alcohol (MA), modified with GOx hyaluronic acid (HA) was developed, namely, CAMGH. It could synchronously interfere including OXPHOS restrict adenosine triphosphate (ATP) supply, achieving inhibition tumors after microwave (MW) thermal therapy. Under low-power MW irradiation, CAMGH induced certain damage while ensuring safety surrounding normal tissues. The loaded consumed glucose tumors, undoubtedly blocking main supply pathway, glycolytic pathway. Then, H

Language: Английский

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Mitochondria‐targeting Bimetallic Cluster Nanozymes Alleviate Neuropathic Pain Through Scavenging ROS and Reducing Inflammation

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

Published: Jan. 29, 2025

Abstract Neuropathic pain is a significant public health concern. Inflammatory mediators and reactive oxygen species (ROS) are recognized as primary contributors to perception. In this study, mitochondria‐targeted modification of bimetallic cluster nanozyme (TPP‐Au‐Ru) developed. This TPP‐Au‐Ru exhibits high affinity for the mitochondrial matrix, effectively scavenging ROS attenuating inflammatory in both vitro vivo settings. Additionally, inhibits activation MAPK NF‐κB signaling cascades protect function. Furthermore, therapeutic dose able alleviate nociceptive symptoms up 36 h with minimal biological toxicity. Therefore, sustained delivery provides an effective long‐lasting approach neuropathic pain. innovative shows promise development more efficient interventions, potentially revolutionizing management enhancing quality life affected individuals.

Language: Английский

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Nanoenhanced‐Cuproptosis Results From the Synergy of Calcium Overload and GSH Depletion with the Increasing of Intracellular Ca/Mn/Cu Ions

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

Published: Feb. 10, 2025

Abstract Cuproptosis is a newly discovered copper‐dependent form of cell death. Intracellular glutathione (GSH) acts as copper chelator to inhibit cuproptosis, so the reduction GSH concentration conducive enhancing cuproptosis cells. In order reduce content and interfere with mitochondrial metabolism, strategy based on calcium overload depletion enhance proposed in this study. Containing manganese (Mn) (Cu) elements, CaCO 3 nanoparticles (NPs) are modified MCF‐7 aptamer (CaCO /Mn/Cu@lip‐Apt). When entering cell, /Mn/Cu@lip‐Apt decomposed released Mn* (Mn 2+ /Mn 3+ 4+ ), Cu Ca . The high valence Mn ion can effectively consume produce which catalyzed H 2 O reactive oxygen species (ROS), while reducing concentration. production ROS promoted influx exogenous large accumulation led intracellular overload, resulting dysfunction metabolism disorders. , turn triggered cuproptosis. This showed excellent antitumor effects provided new way study disease treatment.

Language: Английский

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