Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine

Small, Год журнала: 2024, Номер 20(25)

Опубликована: Янв. 14, 2024

Abstract Ferroptosis is a new form of regulated cell death featuring iron‐dependent lipid peroxides accumulation to kill tumor cells. A growing body evidence has shown the potential ferroptosis‐based cancer therapy in eradicating refractory malignancies that are resistant apoptosis‐based conventional therapies. In recent years, studies have reported number ferroptosis inducers can increase vulnerability cells by regulating ferroptosis‐related signaling pathways. Encouraged rapid development ferroptosis‐driven therapies, interdisciplinary fields combine ferroptosis, pharmaceutical chemistry, and nanotechnology focused. First, prerequisites metabolic pathways for briefly introduced. Then, detail emerging designed boost ferroptosis‐induced therapy, including metal complexes, metal‐based nanoparticles, metal‐free nanoparticles summarized. Subsequently, application synergistic strategies with apoptosis other emphasis on use both cuproptosis induce redox dysregulation intracellular bimetallic copper/iron metabolism disorders during treatment discussed. Finally, challenges associated clinical translation future directions potentiating therapies highlighted.

Язык: Английский

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Copper‐Based Bio‐Coordination Nanoparticle for Enhanced Pyroptosis‐Cuproptosis Cancer Immunotherapy through Redox Modulation and Glycolysis Inhibition

Small, Год журнала: 2025, Номер unknown

Опубликована: Янв. 5, 2025

Copper-based nanoparticles have garnered significant interest in cancer therapy due to their ability induce oxidative stress and cuproptosis cells. However, antitumor effectiveness is constrained by the dynamic redox balance metabolic shift between phosphorylation glycolysis. Here, a polydopamine-coated copper-α-ketoglutaric acid (α-KG) coordination polymer nanoparticle (CKPP) designed for combined pyroptosis-cuproptosis immunotherapy amplifying reactive oxygen species (ROS) production regulating cellular metabolism. The intracellular imbalance achieved through synergistic effects of α-KG-induced mitochondrial reprogramming, photothermally enhanced superoxide dismutase-like activity polydopamine, glutathione depletion copper ions. multifaceted modulation results substantial increase ROS levels, triggering subsequent pyroptosis Furthermore, α-KG shifts metabolism from glycolysis phosphorylation, thereby enhancing induced combination dyshomeostasis inhibition potent enhancement pyroptosis-cuproptosis-mediated therapy. In murine model colorectal cancer, CKPP exhibited remarkable anticancer effect, achieving tumor rate 96.3% complete eradication two out five cases. Overall, this bio-engineered metal-organic nanocomposite demonstrates potential treating immunotherapy.

Язык: Английский

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Biomaterials Elicit Pyroptosis Enhancing Cancer Immunotherapy

Advanced Functional Materials, Год журнала: 2023, Номер 34(7)

Опубликована: Ноя. 5, 2023

Abstract Cancer immunotherapy has the potential to revolutionize treatment of malignant tumors, but its effectiveness is limited by low immune response rate and immune‐related adverse events. Pyroptosis, as an inflammatory programmed cell death type, triggers strong acute antitumor immunity, converting “cold” tumors “hot”. Particularly, biomaterials loading pyroptosis inducers targeting tumor microenvironment engineer pyroptosis, have achieved great progress in recent years. Herein, design strategy, mechanism pathway, role induce cancer are comprehensively reviewed. The present review focuses on application biomaterials‐induced immunotherapy, including nanogel, polymer prodrug, nanovesicle, mesoporous material. Additionally, synthesis a series stimuli‐responsive nanoplatforms, glutathione‐responsive, pH‐responsive, reactive oxygen species‐responsive, enzyme‐mimicking catalytic performance, described. Meanwhile, it augments multiple processes uptake, antigen presentation, T‐cell activation, expansion. Finally, perspectives pyroptosis‐mediated inflammation break through vascular basement membrane barrier achieving efficient volcanic penetration discussed. Artificial intelligence, multi‐omics analysis, anthropogenic animal models organoids presented, aiming provide guidance assistance for constructing effective controllable pyroptosis‐engineered improving immunotherapy.

Язык: Английский

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Advances in covalent organic frameworks for cancer phototherapy

Coordination Chemistry Reviews, Год журнала: 2024, Номер 506, С. 215720 - 215720

Опубликована: Фев. 16, 2024

Язык: Английский

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Monitoring ROS Responsive Fe₃O₄‐based Nanoparticle Mediated Ferroptosis and Immunotherapy via ¹²⁹Xe MRI

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(22)

Опубликована: Март 29, 2024

The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, low response limits immunotherapy efficiency. Here, we report a ROS-responsive Fe

Язык: Английский

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A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Авг. 21, 2024

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation photosensitizers (PSs), many PSs lack specific subcellular targets are limited to first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy essential for strategies. Here, we synthesized four molecules with varying benzene ring numbers thiopyrylium structures preliminarily explore their properties. The near-infrared-II (NIR-II) PS Z1, higher count, exhibited superior ROS generation mitochondria-targeting abilities, large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high (especially type-I ROS) upon 808 nm laser irradiation, leading efficient mitochondria dysfunction combined apoptosis. Moreover, they exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) photoacoustic (PAI). Furthermore, NPs-mediated effectively inhibited growth minimal adverse effects. Our findings offer promising strategy therapy, warranting further preclinical investigations PDT.

Язык: Английский

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Intermetallics triggering pyroptosis and disulfidptosis in cancer cells promote anti-tumor immunity

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 8, 2024

Pyroptosis, an immunogenic programmed cell death, could efficiently activate tumor immunogenicity and reprogram immunosuppressive microenvironment for boosting cancer immunotherapy. However, the overexpression of SLC7A11 promotes glutathione biosynthesis maintaining redox balance countering pyroptosis. Herein, we develop intermetallics modified with glucose oxidase (GOx) soybean phospholipid (SP) as pyroptosis promoters (Pd

Язык: Английский

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Hypoxia-accelerating pyroptosis nanoinducers for promoting image-guided cancer immunotherapy

Biomaterials, Год журнала: 2024, Номер 309, С. 122610 - 122610

Опубликована: Май 11, 2024

Язык: Английский

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Enzyme Immobilization using Covalent Organic Frameworks: From Synthetic Strategy to COFs Functional Role

ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(31), С. 40371 - 40390

Опубликована: Июль 29, 2024

Enzymes, a class of biocatalysts, exhibit remarkable catalytic efficiency, specificity, and selectivity, governing many reactions that are essential for various cascades within living cells. The immobilization structurally flexible enzymes on appropriate supports holds significant importance in facilitating biomimetic transformations extracellular environments. Covalent organic frameworks (COFs) have emerged as ideal candidates enzyme due to high surface tunability, diverse chemical/structural designs, exceptional stability, metal-free nature. Various techniques been proposed fabricate COF-enzyme biocomposites, offering enhancements activity reusability COF-immobilized well new insights into developing advanced enzyme-based applications. In this review, we provide comprehensive overview state-of-the-art strategies immobilizing COFs by focusing their applicability versatility. These systematically summarized compared categorizing them postsynthesis situ immobilization, where respective strengths limitations thoroughly discussed. Combined with an critical emerging applications, further elucidate the multifaceted roles subsequent highlighting biofunctionality achievable through COFs.

Язык: Английский

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Complexity made easy: Aggregation‐induced emission small molecules for cancer diagnosis and phototherapies

Aggregate, Год журнала: 2024, Номер unknown

Опубликована: Сен. 2, 2024

Abstract Phototheranostics has garnered sustained attention due to its significant potential for revolutionizing conventional cancer treatment strategies. While being one of the most commonly employed strategies constructing phototheranostic systems by engineering integration photosensitizers (PSs) into nanosystems, nano‐PSs face challenges including complexity in preparation process, low delivery efficiency, and toxicity issues. Contrastingly, burgeoning popularity small molecule PSs characterized aggregation‐induced emission (AIE) become evident arena phototheranostics. This preference is underscored their well‐defined structures, adjustable photophysical properties, toxicity. Therefore, acquiring profound insights pioneering strides achievable through a solitary PS with AIE tumor phototheranostics paramount scientific significance. In this review, we will discuss recent progress properties diagnosis phototherapies representative examples, guided ethos “Complexity made easy”. We also look forward future development direction molecules, central objective advancing research focal emphasis on simplicity, expeditiousness, safety.

Язык: Английский

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