Ferroptosis Nanomedicine: Clinical Challenges and Opportunities for Modulating Tumor Metabolic and Immunological Landscape

ACS Nano, Год журнала: 2023, Номер 17(16), С. 15328 - 15353

Опубликована: Авг. 13, 2023

Ferroptosis, a type of regulated cell death driven by iron-dependent phospholipid peroxidation, has captured much attention in the field nanomedicine since it was coined 2012. Compared with other modes such as apoptosis and pyroptosis, ferroptosis many distinct features molecular mechanisms cellular morphology, representing promising strategy for treating cancers that are resistant to conventional therapeutic modalities. Moreover, recent insights collectively reveal is tightly connected maintenance tumor immune microenvironment (TIME), suggesting potential application therapies evoking robust antitumor immunity. From biochemical perspective, intricately multiple metabolic pathways, including iron metabolism, lipid redox etc., highlighting importance elucidate relationship between metabolism developing therapies. In this review, we provide comprehensive discussion on current understanding ferroptosis-inducing thoroughly discuss various traits tumors, which offer opportunities direct inhibition through nanointegrated approach. Extending from complex impact TIME, also discussed those important considerations development ferroptosis-based immunotherapy, challenges strategies enhance ferroptosis-enabled immunostimulatory effects while avoiding side effects. We envision study may facilitate translation nanomedicines treatment.

Язык: Английский

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Copper‐Bacteriochlorin Nanosheet as a Specific Pyroptosis Inducer for Robust Tumor Immunotherapy

Advanced Materials, Год журнала: 2023, Номер 35(44)

Опубликована: Июль 8, 2023

Pyroptosis is increasingly considered a new weathervane in cancer immune therapy. However, triggering specific pyroptotic tumor cell death while preserving normal cells still remains major challenge. Herein, brand-new pyroptosis inducer, copper-bacteriochlorin nanosheet (Cu-TBB), designed. The synthesized Cu-TBB can be activated to an "on" state the microenvironment with glutathione (GSH) overexpression, leading release of Cu+ and TBB, respectively. Intriguingly, released drive cascade reactions produce O2-• highly toxic ·OH cells. Additionally, TBB also generate 1 O2 upon 750 nm laser irradiation. Encouragingly, both -driven photodynamic therapy pathways result potent along dendritic maturation T priming, thus simultaneously eliminating primary tumors inhibiting distant growth metastases. Conclusively, well-designed shown trigger vitro vivo, enhanced immunogenicity antitumor efficacy minimizing systemic side effects.

Язык: Английский

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Decomposable Nanoagonists Enable NIR‐Elicited cGAS‐STING Activation for Tandem‐Amplified Photodynamic‐Metalloimmunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 14, 2024

Activation of the cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway has emerged as an efficient strategy to improve therapeutic outcomes immunotherapy. However, "constantly active" mode current STING agonist delivery strategies typically leads off-target toxicity and hyperimmunity. To address this critical issue, herein a metal-organic frameworks-based nanoagonist (DZ@A7) featuring tumor-specific near-infrared (NIR) light-enhanced decomposition is constructed for precisely localized activation photodynamic-metalloimmunotherapy. The engineered enabled generation mitochondria-targeted reactive oxygen species under NIR irradiation specifically release mitochondrial DNA (mtDNA) inhibit repair nuclear via hypoxia-responsive drugs. Oxidized tumor mtDNA serves endogenous danger-associated molecular pattern that activates cGAS-STING pathway. Concurrently, NIR-accelerated zinc ions overloading in cancer cells further enhance cGAS enzymatic activity through metalloimmune effects. By combining synergistically enhanced triggered by irradiation, facilitated maturation dendritic infiltration cytotoxic T lymphocytes primary eradication, which also established long-term anti-tumor immunity suppress metastasis. Therefore, developed NIR-triggered, agonist-free, tandem-amplified pathway, thereby offering distinct paradigm

Язык: Английский

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Nanomaterials‐Induced Redox Imbalance: Challenged and Opportunities for Nanomaterials in Cancer Therapy

Advanced Science, Год журнала: 2024, Номер 11(16)

Опубликована: Фев. 21, 2024

Abstract Cancer cells typically display redox imbalance compared with normal due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This may regulate gene expression, alter protein stability, modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra‐ or extracellular states of cancer at varying state progression trigger programmed death if exceeded a certain threshold, enabling therapeutic selectivity overcoming resistance radiotherapy chemotherapy. Nanotechnology provides new opportunities for modulating their excellent designability high reactivity. Various nanomaterials are widely researched enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, both. Here, physiological features described challenges illustrated. Then, that classified elaborated upon based on ability target regulations. Finally, future perspectives this field proposed. It is hoped review guidance design nanomaterials‐based approaches involving therapy, especially cancers resistant chemotherapy, etc.

Язык: Английский

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Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(21)

Опубликована: Фев. 10, 2024

Abstract Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of tumor itself is a serious obstacle to efficacy. Here, this work reports strategy enhance PCa by triggering cascade self‐enhanced ferroptosis in cells, turning from “hot”. This develops transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness glutathione peroxidase 4 (GPX4) protein targeting. self‐assembles into nanoparticles under aqueous conditions transforms nanofibers response ALP during endosome/lysosome uptake promoting lysosomal membrane permeabilization (LMP). On one hand, released TEP‐FFG‐CRAY target GPX4 selectively degrade light irradiation, inducing ferroptosis; on other large amount leaked Fe 2+ further amplify through Fenton reaction. TEP‐FFG‐CRApY‐induced improves cell maturation dendritic cells (DCs) increasing intratumor T‐cell infiltration. More importantly, recovered T secreting amounts interferon‐gamma (IFN‐γ). provides novel molecular design synergistic molecularly targeted therapy tumors.

Язык: Английский

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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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Ferroptosis: Promising approach for cancer and cancer immunotherapy

Cancer Letters, Год журнала: 2023, Номер 561, С. 216152 - 216152

Опубликована: Апрель 4, 2023

Язык: Английский

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Nanoparticle-mediated synergistic anticancer effect of ferroptosis and photodynamic therapy: novel insights and perspectives

Asian Journal of Pharmaceutical Sciences, Год журнала: 2023, Номер 18(4), С. 100829 - 100829

Опубликована: Июль 1, 2023

Current antitumor monotherapy has many limitations, highlighting the need for novel synergistic anticancer strategies. Ferroptosis is an iron-dependent form of nonapoptotic cell death that plays a pivotal regulatory role in tumorigenesis and treatment. Photodynamic therapy (PDT) causes irreversible chemical damage to target lesions widely used therapy. However, PDT's effectiveness usually hindered by several obstacles, such as hypoxia, excess glutathione (GSH), tumor resistance. improves efficacy PDT increasing oxygen reactive species (ROS) or reducing GSH levels, also enhances ferroptosis induction due ROS effect microenvironment (TME). Strategies based on nanoparticles (NPs) can subtly exploit potential synergy PDT. This review explores recent advances current challenges landscape underlying mechanisms regulating PDT, well nano delivery system-mediated activity. These include polymers, biomimetic materials, metal organic frameworks (MOFs), inorganics, carrier-free NPs. Finally, we highlight future perspectives this emerging paradigm targeted cancer therapies.

Язык: Английский

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Nanoenabled Intracellular Metal Ion Homeostasis Regulation for Tumor Therapy

Advanced Science, Год журнала: 2023, Номер 11(7)

Опубликована: Дек. 8, 2023

Abstract Endogenous essential metal ions play an important role in many life processes, especially tumor development and immune response. The approval of various metallodrugs for therapy brings more attention to the antitumor effect ions. With deepening understanding regulation mechanisms ion homeostasis vivo, breaking intracellular becomes a new means inhibit proliferation cells activate Diverse nanomedicines with loading small molecular regulators or have been developed disrupt cells, higher safety efficiency than free compounds. This comprehensive review focuses on latest progress regulation‐based including calcium (Ca 2+ ), ferrous (Fe cuprous (Cu + managanese (Mn zinc (Zn ). physiological functions processes are summarized guide design nanomedicines. Then ions‐based some efficient synergistic therapies highlighted. Finally, challenges future developments also discussed, hoping provide reference finding effective therapies.

Язык: Английский

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Recent advances in Fenton and Fenton-like reaction mediated nanoparticle in cancer therapy

Biomedical Technology, Год журнала: 2023, Номер 3, С. 40 - 51

Опубликована: Янв. 23, 2023

Fenton and like reaction have been well clarified as efficient reactive oxygen species (ROS) sources in tumor, widely developed into a cancer treatment method. Meanwhile, transition metal-based nanomaterials with or characteristics also explored therapeutic agents for the therapy, mainly chemo-dynamic ferroptosis induced therapy. Herein,to summarize recent advances mediated nanoparticles this minireview, we first introduced mechanisms of two methods based on reaction, then well-designed Fenton-like therapies. Finally its challenges perspectives are discussed.

Язык: Английский

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