A Noble AuPtAg‐GOx Nanozyme for Synergistic Tumor Immunotherapy Induced by Starvation Therapy‐Augmented Mild Photothermal Therapy

Advanced Science, Journal Year: 2022, Volume and Issue: 9(31)

Published: Sept. 25, 2022

Abstract Notwithstanding immune checkpoint blocking (ICB) therapy has made eminent clinical breakthroughs, overcoming immunologically “cold” tumors remains challenging. Here, a cascade potentiated nanomodulator AuPtAg‐GOx is engineered for boosting responsiveness. Upon 1064 nm laser irradiation, AuPtAg‐mediated mild photothermal (PTT) activates cytotoxic T lymphocytes and reverses the immunogenic tumor microenvironment. Further, to amplify thermal sensitivity of cells, glucose oxidase (GOx) introduced suppress production heat shock proteins, thereby promoting therapy. Complementarily, AuPtAg nanozymes with catalase‐like activity can ameliorate hypoxia, significantly improving GOx activity. As result, combination self‐augmented ability PD‐L1 antibody further escalate antitumor efficacy. The AuPtAg‐GOx‐based synergistic starvation therapy, PTT, immunotherapy enhancement strategy be favorable tool effectively kill cancer cells.

Language: Английский

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Multi-enzyme Co-expressed Dual-Atom Nanozymes Induce Cascade Immunogenic Ferroptosis via Activating Interferon-γ and Targeting Arachidonic Acid Metabolism

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(16), P. 8965 - 8978

Published: April 14, 2023

Immunotherapy is currently the most promising treatment strategy for long-term tumor regression. However, current cancer immunotherapy shows low response rates due to insufficient immunogenicity of cells. Herein, we report a keep cells highly immunogenic by triggering cascade ferroptosis. We developed six-enzyme co-expressed nanoplatform: lipoxygenase (LOX) and phospholipase A2 (PLA2)-co-loaded FeCo/Fe-Co dual-metal atom nanozyme (FeCo/Fe-Co DAzyme/PL), which can not only induce initial ferroptosis through its own multi-enzyme mimetic activities but also up-regulate arachidonic acid (AA) expression synergize with CD8+ T cell-derived IFN-γ ACSL4-mediated During this process, DAzyme/PL lipid peroxidation (LPO) efficiently generating reactive oxygen species (ROS) depleting GSH GPX4 at sites. Additionally, free AA released from PLA2 catalysis converted into arachidonyl-CoA under activation ACSL4 stimulated IFN-γ, further incorporated phospholipids on membranes peroxidized participation LOX. Consequently, promote irreversible multiple ROS storms, GSH/GPX4 depletion, LOX catalysis, IFN-γ-mediated activation, constructing an effective pathway overcome drawbacks immunotherapy.

Language: Английский

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Ferroptosis as a potential target for cancer therapy

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 24, 2023

Abstract Ferroptosis is a recently discovered essential type of cell death that mainly characterized by iron overload and lipid peroxidation. Emerging evidence suggests ferroptosis double-edged sword in human cancer. However, the precise underlying molecular mechanisms their differential roles tumorigenesis are unclear. Therefore, this review, we summarize briefly present key pathways ferroptosis, paying special attention to regulation as well its dual role an oncogenic tumor suppressor event various cancers. Moreover, multiple pharmacological activators summarized, prospect targeting cancer therapy further elucidated.

Language: Английский

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A photo-triggered self-accelerated nanoplatform for multifunctional image-guided combination cancer immunotherapy

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 25, 2023

Precise and efficient image-guided immunotherapy holds great promise for cancer treatment. Here, we report a self-accelerated nanoplatform combining an aggregation-induced emission luminogen (AIEgen) hypoxia-responsive prodrug multifunctional combination immunotherapy. The near-infrared AIEgen with methoxy substitution simultaneously possesses boosted fluorescence photoacoustic (PA) brightness the strong light absorption ability, as well amplified type I II photodynamic therapy (PDT) properties via enhanced intersystem crossing process. By formulating high-performance paclitaxel (PTX) into nanoparticles, further camouflaging macrophage cell membrane, tumor-targeting theranostic agent is built. integration of PA imaging helps to delineate tumor site sensitively, providing accurate guidance light-induced PDT effect could consume local oxygen lead severer hypoxia, accelerating release PTX drug. As result, chemotherapy induces immunogenic death, which not only elicit antitumor immunity suppress primary tumor, but also inhibit growth distant in 4T1 tumor-bearing female mice. strategy develop agents rational molecular design boosting

Language: Английский

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Emerging Strategies in Stimuli-Responsive Prodrug Nanosystems for Cancer Therapy

ACS Nano, Journal Year: 2022, Volume and Issue: 16(9), P. 13513 - 13553

Published: Sept. 1, 2022

Prodrugs are chemically modified drug molecules that inactive before administration. After administration, they converted in situ to parent drugs and induce the mechanism of action. The development prodrugs has upgraded conventional treatments terms bioavailability, targeting, reduced side effects. Especially cancer therapy, application achieved substantial therapeutic From serendipitous discovery early stage functional design with pertinence nowadays, importance is self-evident. At present, studying stimuli-responsive activation mechanisms, regulating stimuli intensity vivo, designing nanoscale prodrug formulations major strategies promote prodrugs. In this review, we provide an outlook recent cutting-edge studies on nanosystems from these three aspects. We also discuss prospects challenges future such

Language: Английский

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Semiconducting Polymer Nanoparticles with Surface‐Mimicking Protein Secondary Structure as Lysosome‐Targeting Chimaeras for Self‐Synergistic Cancer Immunotherapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(31)

Published: June 15, 2022

Immunotherapy has received tremendous attention for tumor treatment, but the efficacy is greatly hindered by insufficient tumor-infiltration of immune cells and immunosuppressive microenvironment. The strategy that can efficiently activate cytotoxic T lymphocytes inhibit negative regulators will amplify immunotherapy outcome, which however very rare. Herein, a new kind semiconducting polymer (SP) nanoparticles developed, featured with surface-mimicking protein secondary structure (SPSS NPs) self-synergistic cancer combining immunogenic cell death (ICD) checkpoint blockade therapy. SPs excellent photodynamic property are synthesized rational fluorination, massively induce ICD. Additionally, peptide antagonists introduced self-assembled into β-sheet structures on NP surface via preparation process optimization, function as efficient lysosome-targeting chimaeras (LYTACs) to mediate degradation programmed ligand-1 (PD-L1) in lysosome. In vivo experiments demonstrate SPSS NPs not only elicit strong antitumor immunity suppress both primary distant tumor, also evoke long-term immunological memory against rechallenge. This work introduces robust agents well-designed photosensitizer-based ICD induction structures-mediated LYTAC-like multivalence PD-L1 blockade, rendering great promise synergistic immunotherapy.

Language: Английский

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Intracellular Self‐Assembly Driven Nucleus‐Targeted Photo‐Immune Stimulator with Chromatin Decompaction Function for Robust Innate and Adaptive Antitumor Immunity

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(17)

Published: March 4, 2022

Abstract Efficient nuclear DNA damage and release is highly recommended to improve the photodynamic immunotherapy by eliciting innate immune response yet remains challenging. Herein, an intracellular self‐assembly driven nucleus‐targeted photo‐immune stimulator (PIS) with chromatin decompaction function reported for adaptive antitumor immunity co‐activation. The PIS consists of vorinostat (SAHA)‐loaded manganese‐porphyrin metal‐organic framework (Mn (III)‐TCPP MOF) further modification AS1411 aptamer. can be efficiently internalized tumor cells disassembled under overexpressed glutathione (GSH). Notably, released able self‐assembled photosensitizer TCPP in situ within cells, driving delivery TCPP; meanwhile, loaded SAHA induce decompaction, cooperatively promoting TCPP‐mediated cytosolic laser irradiation. In addition, manganese ions 2+ ) enhance DNA/cyclic GMP‐AMP synthase (cGAS)‐stimulator interferon gene (STING) pathway mediated immunity, which synergizes PDT‐induced immunogenic cell death achieve co‐activation immunity. Compared traditional PDT, PDT system show significantly enhanced efficacy inhibiting primary growth distant metastasis several xenograft models, mechanistically maturation dendritic infiltration natural killer cell, cytotoxic T lymphocytes.

Language: Английский

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CYP1B1 inhibits ferroptosis and induces anti-PD-1 resistance by degrading ACSL4 in colorectal cancer

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 14, 2023

Abstract Immune checkpoint blockade (ICB) is a promising treatment strategy for colorectal cancer (CRC) patients. However, most CRC patients do not response well to ICB therapy. Increasing evidence indicates that ferroptosis plays critical role in immunotherapy. efficacy may be enhanced by inducing tumor ferroptosis. Cytochrome P450 1B1 (CYP1B1) metabolic enzyme participates arachidonic acid metabolism. the of CYP1B1 remains unclear. In this study, we demonstrated derived 20-HETE activated protein kinase C pathway increase FBXO10 expression, which turn promoted ubiquitination and degradation acyl-CoA synthetase long-chain family member 4 (ACSL4), ultimately cells resistance Furthermore, inhibiting sensitized anti-PD-1 antibody mouce model. addition, expression was negatively correlated with ACSL4 high poor prognosis CRC. Taken together, our work identified as potential biomarker enhancing therapy

Language: Английский

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Ferroptosis: principles and significance in health and disease

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: June 6, 2024

Abstract Ferroptosis, an iron-dependent form of cell death characterized by uncontrolled lipid peroxidation, is governed molecular networks involving diverse molecules and organelles. Since its recognition as a non-apoptotic pathway in 2012, ferroptosis has emerged crucial mechanism numerous physiological pathological contexts, leading to significant therapeutic advancements across wide range diseases. This review summarizes the fundamental mechanisms regulatory pathways underlying ferroptosis, including both GPX4-dependent -independent antioxidant mechanisms. Additionally, we examine involvement various conditions, cancer, neurodegenerative diseases, sepsis, ischemia–reperfusion injury, autoimmune disorders, metabolic disorders. Specifically, explore role response chemotherapy, radiotherapy, immunotherapy, nanotherapy, targeted therapy. Furthermore, discuss pharmacological strategies for modulating potential biomarkers monitoring this process. Lastly, elucidate interplay between other forms regulated death. Such insights hold promise advancing our understanding context human health disease.

Language: Английский

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Prospects, advances and biological applications of MOF-based platform for the treatment of lung cancer

Biomaterials Science, Journal Year: 2024, Volume and Issue: 12(15), P. 3725 - 3744

Published: Jan. 1, 2024

Herein, we reviewed the recent development in use of MOF materials as a platform for treatment lung cancer.

Language: Английский

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