Boosting Energy Deprivation by Synchronous Interventions of Glycolysis and Oxidative Phosphorylation for Bioenergetic Therapy Synergetic with Chemodynamic/Photothermal Therapy

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Март 15, 2024

Abstract Bioenergetic therapy is emerging as a promising therapeutic approach. However, its effectiveness restricted by metabolic plasticity, tumor cells switch phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) to compensate for energy. Herein, Metformin (MET) BAY‐876 (BAY) co‐loaded CuFe 2 O 4 (CF) nanoplatform (CFMB) developed boost energy deprivation synchronous interventions of OXPHOS bioenergetic synergetic with chemodynamic/photothermal (CDT/PTT). The MET can simultaneously restrain inhibiting hexokinase (HK2) activity damaging mitochondrial function deprive energy, respectively. Besides, BAY blocks glucose uptake transporter 1 (GLUT1) expression, further potentiating the repression thus achieving much more depletion tumorigenic sources. Interestingly, upregulated antioxidant glutathione (GSH) in cancer triggers CFMB degradation release Cu + /Fe 2+ catalyzing tumor‐overexpressed H hydroxyl radical (∙OH), both impairing GSH‐depletion amplified CDT. Furthermore, upon near‐infrared (NIR) light irradiation, has photothermal conversion capacity kill PTT improve ∙OH production enhanced In vivo experiments have manifested that remarkably suppressed growth mice without systemic toxicity. This study provides new modality paradigm bioenergetic‐related therapies.

Язык: Английский

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Electret‐Inspired Charge‐Injected Hydrogel for Scar‐Free Healing of Bacterially Infected Burns Through Bioelectrical Stimulation and Immune Modulation

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Abstract In this study, an electret‐inspired, charge‐injected hydrogel called QOSP (QCS/OD/SDI/PANI/PS/Plasma) that promotes scar‐free healing of bacteria‐infected burns through bioelectrical stimulation and immune modulation, is presented. The hydrogel, composed quaternized chitosan (QCS), oxidized dextran (OD), sulfadiazine (SDI), polystyrene (PS), polyaniline nanowires (PANI), forms a conductive network capable storing releasing electric charges, emulating electret‐like mechanism. This structure delivers signals continuously, enhancing wound by regulating responses minimizing fibrosis. mouse model second‐degree infected with Staphylococcus aureus (SA) Pseudomonas aeruginosa (PA), the accelerates 32% reduces bacterial load 60%, significantly inhibited scar formation 40% compared to controls. modulates Th1/Th2 balance toward Th1‐dominant antifibrotic state chitosan, thereby reducing collagen deposition 35%. Electro‐dielectric characterization reveals dielectric constant 6.2, 34% improvement in conductivity (3.33 × 10 −5 S/m) 30 °C increase thermal stability. Proteomic analysis highlights 50% down‐regulation pro‐inflammatory pro‐fibrotic pathways, suggesting controlled response conducive healing. study underscores potential bioelectrically active hydrogels as novel approach for treating wounds prone scarring.

Язык: Английский

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Synchronously Evoking Disulfidptosis and Ferroptosis via Systematical Glucose Deprivation Targeting SLC7A11/GSH/GPX4 Antioxidant Axis

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Disulfidptosis and ferroptosis are recently identified programmed cell deaths for tumor therapy, both of which highly depend on the intracellular cystine/cysteine transformation cystine transporter solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (SLC7A11/GSH/GPX4) antioxidant axis. However, disulfidptosis usually asynchronous due to opposite effect transport them. Herein, systematic glucose deprivation, by inhibiting upstream uptake promoting downstream consumption, is proposed synchronously evoke ferroptosis. As an example, Au nanodots Fe-apigenin (Ap) complexes coloaded FeOOH nanoshuttles (FeOOH@Fe-Ap@Au NSs) employed regulate SLC7A11/GSH/GPX4 axis performing disulfidptosis- ferroptosis-mediated therapy synchronously. In this scenario, exhibit oxidase-like activity when consuming massive glucose. Meanwhile, Ap can inhibit downregulating 1, depriving fundamentally. The systematical deprivation limits supplement NADPH suppresses axis, thus solving contradiction addition, efficient delivery exogenous iron ions FeOOH@Fe-Ap@Au NSs self-supplied H2O2 through nanodots-catalytic oxidation facilitate Fenton reaction therewith help amplify a result synchronous occurrence ferroptosis, good efficacy in ovarian cancer therapeutic model.

Язык: Английский

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NIR-triggered and Thermoresponsive Core-shell nanoparticles for synergistic anticancer therapy

Journal of Controlled Release, Год журнала: 2024, Номер 374, С. 194 - 204

Опубликована: Авг. 15, 2024

Язык: Английский

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Tumor microenvironment activation amplify oxidative stress promoting tumor energy remodeling for mild photothermal therapy and cuproptosis

Redox Biology, Год журнала: 2024, Номер 75, С. 103260 - 103260

Опубликована: Июнь 28, 2024

Tumor metabolic reprogramming requires high levels of adenosine triphosphate (ATP) to maintain treatment resistance, which poses major challenges chemotherapy and photothermal therapy. Especially, ATP promote copper ion efflux for limiting the curative effect cuproptosis. Here, an H

Язык: Английский

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Boosting ferroptosis by intervention of redox balance and synergetic with photothermal/photodynamic therapy for suppression of pancreatic cancer

Chemical Engineering Journal, Год журнала: 2024, Номер 497, С. 154569 - 154569

Опубликована: Авг. 5, 2024

Язык: Английский

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Synergistic enhancement of low-dose radiation therapy via cuproptosis and metabolic reprogramming for radiosensitization in in situ hepatocellular carcinoma

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Дек. 19, 2024

Radiotherapy (RT) is a primary clinical approach for cancer treatment, but its efficacy often hindered by various challenges, especially radiation resistance, which greatly compromises the therapeutic effectiveness of RT. Mitochondria, central to cellular energy metabolism and regulation cell death, play critical role in mechanisms radioresistance. In this context, cuproptosis, novel copper-induced mitochondria-respiratory-dependent death pathway, offers promising avenue radiosensitization. study, an innovative theranostic nanoplatform was designed induce cuproptosis synergy with low-dose therapy (LDRT, i.e., 0.5–2 Gy) treatment situ hepatocellular carcinoma (HCC). This aims reverse hypoxic tumor microenvironment, promoting shift from glycolysis oxidative phosphorylation (OXPHOS), thereby enhancing sensitivity cuproptosis. Concurrently, Fenton-like reaction ensures sustained supply copper depletion glutathione (GSH), inducing disrupting mitochondrial function, interrupting supply. strategy effectively overcomes radioresistance enhances against tumors. conclusion, study elucidates intricate interactions among hypoxia reversal, metabolic reprogramming, radiosensitization, particularly context treating carcinoma, providing paradigm radiotherapy.

Язык: Английский

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Tailored Biomimetic Nanoreactor Improves Glioma Chemodynamic Treatment via Triple Glutathione Depletion and Prompt Acidity Elevation

Materials Today Bio, Год журнала: 2025, Номер 30, С. 101447 - 101447

Опубликована: Янв. 5, 2025

Chemodynamic therapy (CDT) is an emerging antitumor strategy utilizing iron-initiated Fenton reaction to destroy tumor cells by converting endogenous H2O2 into highly toxic hydroxyl radical (OH). However, the intratumoral overexpressed glutathione (GSH) and deficient acid greatly reduce CDT efficacy because of OH scavenging decreased production efficiency. Even worse, various physiological barriers, especially in glioma, further put brakes on targeted delivery agents. Herein, exploring thiol potential 5,5'-dithiobis-2-nitrobenzoic (DTNB), we have constructed a tailored biomimetic nanoreactor improve glioma through synchronous GSH exhaustion acidity elevation. The was fabricated employing DTNB drive nano-assembly BSA molecules, followed loading carrier onto cell surface neutrophils via disulfide-thiol exchange. Upon sensing inflammatory signal, hijacked efficiently targets site, which then dually depletes disulfide bond stabilizing nanostructure following liberated Fe (III). In particular, simultaneously released can not only consume residual GSH, but also produce 5-thio-2-nitrobenzoic (TNB) promptly, resulting accelerated reaction. Through vitro vivo experiments, demonstrate exhaustive regulation chemistry could potentially serve as novel for glioma.

Язык: Английский

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Fabrication of temozolomide-loaded polydopamine-coated copper ferrite clocked bovine serum albumin nanoparticles delivery for glioma cancer and induction of apoptosis mechanism

Journal of Drug Delivery Science and Technology, Год журнала: 2025, Номер unknown, С. 106642 - 106642

Опубликована: Янв. 1, 2025

Язык: Английский

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Anti‐Tumor Strategies Targeting Nutritional Deprivation: Challenges and Opportunities

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 2, 2025

Higher and richer nutrient requirements are typical features that distinguish tumor cells from AU: cells, ensuring adequate substrates energy sources for cell proliferation migration. Therefore, deprivation strategies based on targeted technologies can induce impaired viability in which more sensitive than normal cells. In this review, nutrients required by related metabolic pathways introduced, anti-tumor developed to target described. addition the nutritional characteristics of other microenvironment (including macrophages, neutrophils, natural killer T cancer-associated fibroblasts) new also summarized. conclusion, recent advances targeting blockade reviewed, challenges prospects these discussed, theoretical significance optimizing clinical application nutrition strategies.

Язык: Английский

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