Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 312 - 312

Published: March 1, 2024

Since the evolution of aerobic metabolism, reactive oxygen species (ROS) have represented significant challenges to diverse life forms. In recent decades, increasing knowledge has revealed a dual role for ROS in cell physiology, showing they serve as major source cellular damage while also functioning important signaling molecules various biological processes. Our understanding homeostasis and ROS-mediated pathways presumed that are ancient highly conserved mechanisms shared by most organisms. However, emerging evidence highlights complexity plasticity signaling, particularly animals evolved extreme environments. this review, we focus on generation, antioxidative systems main influenced ROS. addition, discuss ROS’s responsive transcription regulation how it may been shaped over course evolution.

Language: Английский

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Drug-induced oxidative stress in cancer treatments: Angel or devil?

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102754 - 102754

Published: May 18, 2023

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one the most significant biological events cancer progression. Cancer cells generally represent a higher level, which suggests dual therapeutic strategy by regulating status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, exhibits great anti-cancer capability, attributing to accumulation within cells, whereas restore homeostasis has been claimed fail several clinical practices. Targeting vulnerability pro-oxidants capable generating excessive reactive oxygen species (ROS) surfaced an important strategy. However, multiple adverse effects caused indiscriminate attacks uncontrolled drug-induced OS on normal tissues and drug-tolerant capacity some certain greatly limit their further applications. Herein, we review representative oxidative drugs summarize side organs, emphasizing that seeking balance between damage value exploiting next-generation OS-based chemotherapeutics.

Language: Английский

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Cuproptosis: Harnessing Transition Metal for Cancer Therapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(20), P. 19581 - 19599

Published: Oct. 11, 2023

Transition metal elements, such as copper, play diverse and pivotal roles in oncology. They act constituents of metalloenzymes involved cellular metabolism, function signaling molecules to regulate the proliferation metastasis tumors, are integral components metal-based anticancer drugs. Notably, recent research reveals that excessive copper can also modulate occurrence programmed cell death (PCD), known cuprotosis, cancer cells. This modulation occurs through disruption tumor metabolism induction proteotoxic stress. discovery uncovers a mode interaction between transition metals proteins, emphasizing intricate link homeostasis metabolism. Moreover, they provide innovative therapeutic strategies for precise diagnosis treatment malignant tumors. At crossroads chemistry oncology, we undertake comprehensive review elucidating molecular mechanisms underpinning cuproptosis. Additionally, summarize current nanotherapeutic approaches target cuproptosis an overview available laboratory clinical methods monitoring this process. In context emerging concepts, challenges, opportunities, emphasize significant potential nanotechnology advancement field.

Language: Английский

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Boosting Ferroptosis Therapy with Iridium Single‐Atom Nanocatalyst in Ultralow Metal Content

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(17)

Published: Jan. 31, 2023

Nanocatalysts are promising tumor therapeutics due to their ability induce reactive oxygen species in the microenvironment. Although increasing metal loading can improve catalytic activity, quandary of high content versus potential systemic biotoxicity remains challenging. Here, a fully exposed active site strategy by site-specific anchoring single iridium (Ir) atoms on outer surface nitrogen-doped carbon composite (Ir single-atom catalyst (SAC)) is reported achieve remarkable performance at ultralow (≈0.11%). The Ir SAC exhibits prominent dual enzymatic activities mimic peroxidase and glutathione peroxidase, which catalyzes conversion endogenous H2 O2 into •OH acidic TME depletes (GSH) simultaneously. With an advanced support GSH-trapping platinum(IV) encapsulation with red-blood-cell membrane, this nanocatalytic agent (Pt@IrSAC/RBC) causes intense lipid peroxidation that boosts cell ferroptosis. Pt@IrSAC/RBC demonstrates superior therapeutic efficacy mouse triple-negative mammary carcinoma model, resulting complete ablation treatment session negligible side effects. These outcomes may provide valuable insights design nanocatalysts biosafety for biomedical applications.

Language: Английский

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Lysosomal Rupture‐Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High‐Efficiency Cancer Immunotherapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(29)

Published: Feb. 23, 2024

Abstract Autophagy, a lysosome‐involved degradation pathway, as self‐protective cellular process, always weakens the efficiency of tumor therapies. Herein, for first time, biodegradable copper (Cu) ions doped layered double hydroxide (Cu‐LDH) nanoparticles are reported cancer immunotherapy via lysosomal rupture‐mediated “Broken Window Effect”. Only injection Cu‐LDH single therapeutic agent achieves various organelles destruction after rupture, well abnormal aggregation Cu in cells cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by rupture improves overload‐mediated pyroptosis blocking lysosome‐mediated bulk leading to good anti‐tumor immune responses ultimately high‐efficiency growth inhibition. This Effect” provides new paradigm enhanced therapy.

Language: Английский

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pH/GSH dual responsive nanosystem for nitric oxide generation enhanced type I photodynamic therapy

Bioactive Materials, Journal Year: 2024, Volume and Issue: 34, P. 414 - 421

Published: Jan. 10, 2024

Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive tumor microenvironment (TME) enhance PDT through glutathione (GSH) depletion. Our approach aims expand sources therapeutic benefits by promoting generation superoxide radicals (O

Language: Английский

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A non‐metal single atom nanozyme for cutting off the energy and reducing power of tumors

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(16)

Published: Feb. 16, 2024

Enzymes are considered safe and effective therapeutic tools for various diseases. With the increasing integration of biomedicine nanotechnology, artificial nanozymes offer advanced controllability functionality in medical design. However, several notable gaps, such as catalytic diversity, specificity biosafety, still exist between their native counterparts. Here we report a non-metal single-selenium (Se)-atom nanozyme (SeSAE), which exhibits potent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mimetic activity. This novel single atom provides alternative to conventional metal-based catalysts effectively cuts off cellular energy reduction equivalents through its distinctive function tumors. In this study, have demonstrated substantial efficacy SeSAE an antitumor nanomedicine across diverse mouse models without discernible systemic adverse effects. The mechanism NADPH oxidase-like activity was rationalized by density functional theory calculations. Furthermore, comprehensive elucidation biological functions, cell death pathways, metabolic remodeling effects conducted, aiming provide valuable insights into development with clinical translation potential.

Language: Английский

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Cell Membrane as A Promising Therapeutic Target: From Materials Design to Biomedical Applications

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: Feb. 19, 2024

The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction information exchange. Therefore, disrupting its structure or impairing functions can potentially cause irreversible damage. Presently, the tumor recognized as promising therapeutic target for various treatment methods. Given extensive research focused on membranes, it both necessary timely to discuss these developments, from materials design specific biomedical applications. This review covers treatments based functional targeting membrane, ranging well-known membrane-anchoring photodynamic therapy recent lysosome-targeting chimaeras protein degradation. diverse mechanisms are introduced in following sections: phototherapy, self-assembly situ biosynthesis degradation proteins by chimeras. In each section, we outline conceptual general derived numerous studies, emphasizing representative examples understand advancements draw inspiration. Finally, some challenges future directions membrane-targeted our perspective. aims engage multidisciplinary readers encourage researchers related fields advance fundamental theories practical applications membrane-targeting agents.

Language: Английский

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In Situ Mitochondrial Biomineralization for Drug‐Free Cancer Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 7, 2024

The common clinical chemotherapy often brings serious side effects to patients, mainly due the off-target and leakage of toxic drugs. However, this is fatal for some specific tumors, such as brain tumors neuroma. This study performs a drug-free approach by encapsulating black phosphorus (BP) calcium peroxide (CaO

Language: Английский

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Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(4), P. 1742 - 1758

Published: Dec. 16, 2023

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to activation cellular oxidative stress and immune responses. While role in promoting inflammation hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which composed oxaliplatin (Oxa) acetaminophen (APAP), enhance anti-tumor amplify response. Our findings demonstrate that OAP2 induces nuclear damage, resulting production DNA. Additionally, downregulates expression Sam50, promote mtDNA secretion, double-stranded accumulation ultimately synergistically activating intracellular cGAS-STING pathway. The induced by overcomes limitations Oxa STING pathway simultaneously promotes gasdermin-D-mediated cell pyroptosis. also dendritic maturation enhances quantity efficacy cytotoxic T cells, thereby inhibiting cancer proliferation metastasis. Briefly, our study introduces first small-molecule inhibitor regulates for active immunotherapy research, may provide creative idea targeting organelle therapy.

Language: Английский

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