A Self‐Amplifying ROS‐Responsive Nanoplatform for Simultaneous Cuproptosis and Cancer Immunotherapy

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

Опубликована: Апрель 3, 2024

Abstract Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as efficient ionophore can specifically transport into mitochondria and trigger cuproptosis. However, ES be rapidly removed metabolized during intravenous administration, leading to a short half‐life limited tumor accumulation, which hampers its clinical application. Here, study develops reactive oxygen species (ROS)‐responsive polymer (PCP) based cinnamaldehyde (CA) polyethylene glycol (PEG) encapsulate ES‐Cu compound (EC), forming ECPCP. ECPCP significantly prolongs systemic circulation of EC enhances accumulation. After cellular internalization, PCP coating stimulatingly dissociates exposing high‐level ROS, releases Cu, thereby triggering via Meanwhile, 2+ ‐stimulated Fenton‐like reaction together with CA‐stimulated ROS production simultaneously breaks redox homeostasis, compensates for insufficient oxidative stress treated alone, in turn inducing immunogenic cells, achieving simultaneous cuproptosis immunotherapy. Furthermore, excessive accelerates stimuli‐dissociation ECPCP, positive feedback therapy loop against self‐alleviation. Therefore, nanoplatform immunotherapy improves dual antitumor mechanism provides potential optimization

Язык: Английский

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Genetically Edited Cascade Nanozymes for Cancer Immunotherapy

ACS Nano, Год журнала: 2024, Номер 18(19), С. 12295 - 12310

Опубликована: Май 2, 2024

Immune checkpoint blockade (ICB) has brought tremendous clinical progress, but its therapeutic outcome can be limited due to insufficient activation of dendritic cells (DCs) and infiltration cytotoxic T lymphocytes (CTLs). Evoking immunogenic cell death (ICD) is one promising strategy promote DC maturation elicit T-cell immunity, whereas low levels ICD induction solid tumors restrict durable antitumor efficacy. Herein, we report a genetically edited membrane-coated cascade nanozyme (gCM@MnAu) for enhanced cancer immunotherapy by inducing activating the stimulator interferon genes (STING) pathway. In tumor microenvironment (TME), gCM@MnAu initiates reaction generates abundant hydroxyl (•OH), resulting in improved chemodynamic therapy (CDT) boosted activation. addition, released Mn

Язык: Английский

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Reactive Oxygen Species Amplifier for Apoptosis-Ferroptosis Mediated High-Efficiency Radiosensitization of Tumors

ACS Nano, Год журнала: 2024, Номер 18(14), С. 10288 - 10301

Опубликована: Апрель 1, 2024

Insufficient reactive oxygen species (ROS) production and radioresistance have consistently contributed to the failure of radiotherapy (RT). The development a biomaterial capable activating ROS-induced apoptosis ferroptosis is potential strategy enhance RT sensitivity. To achieve precision high-efficiency RT, theranostic nanoplatform Au/Cu nanodots (Au/CuNDs) were designed for dual-mode imaging, amplifying ROS generation, inducing apoptosis-ferroptosis sensitize RT. A large amount derived from three aspects: (1) When exposed ionizing radiation, Au/CuNDs effectively absorb photons emit various electrons, which can interact with water produce ROS. (2) act as catalase-like abundant through Fenton reaction hydrogen peroxide overexpressed tumor cells. (3) deplete glutathione, causes accumulation Large amounts radiation further lead by increasing DNA damage, enhancing lipid peroxidation, significantly improving therapeutic efficiency Furthermore, serve an excellent nanoprobe high-resolution near-infrared fluorescence imaging computed tomography tumors. promising performance shows their application in clinical cancer detection imaging-guided minimizing damage adjacent normal tissues during In summary, our developed integrates sensitizes via ROS-activated apoptosis-ferroptosis, offering prospect diagnosis treatment.

Язык: Английский

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An Intelligent Cupreous Nanoplatform with Self-Supplied H₂O₂ and Cu²⁺/Cu⁺ Conversion to Boost Cuproptosis and Chemodynamic Combined Therapy

Chemistry of Materials, Год журнала: 2024, Номер 36(2), С. 815 - 828

Опубликована: Янв. 11, 2024

Cuproptosis is a newly identified copper-dependent cell death and holds great promise for cancer therapy. However, transporting enough copper into cells challenge. Herein, an intelligent cupreous nanoplatform (denoted as CuO2-MSN@TA-Cu2+), consisting of in situ formation CuO2 within mesoporous silica nanoparticles (MSN) then deposition with tannic acid (TA)-Cu2+ complex, designed developed to realize on-demand delivery cuproptosis-based combination CuO2-MSN@TA-Cu2+ exhibits tumor microenvironment-triggered therapeutic activity, wherein the outer TA-Cu2+ complex readily disassembled release Cu2+ liberate internal produce H2O2. The overloaded can not only directly convert endogenous H2O2 self-supplied highly toxic hydroxyl radicals chemodynamic therapy (CDT) via Cu-based Fenton-like reaction but also undergo glutathione-mediated reduction Cu+ species induce potent cellular cuproptosis enhance CDT. experimental results indicate that produces remarkable cytotoxicity against significantly suppresses growth by 93.42% mice-bearing 4T1 breast tumors. This work provides new paradigm boost cuproptosis-related may inspire design advanced nanoplatforms.

Язык: Английский

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A strategy of “adding fuel to the flames” enables a self-accelerating cycle of ferroptosis-cuproptosis for potent antitumor therapy

Biomaterials, Год журнала: 2024, Номер 311, С. 122701 - 122701

Опубликована: Июль 6, 2024

Язык: Английский

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Dendrimer/metal-phenolic nanocomplexes encapsulating CuO2 for targeted magnetic resonance imaging and enhanced ferroptosis/cuproptosis/chemodynamic therapy by regulating the tumor microenvironment

Acta Biomaterialia, Год журнала: 2024, Номер 183, С. 252 - 263

Опубликована: Май 25, 2024

Язык: Английский

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Spatially Asymmetric Nanoparticles for Boosting Ferroptosis in Tumor Therapy

Nano Letters, Год журнала: 2024, Номер 24(4), С. 1284 - 1293

Опубликована: Янв. 17, 2024

Despite its effectiveness in eliminating cancer cells, ferroptosis is hindered by the high natural antioxidant glutathione (GSH) levels tumor microenvironment. Herein, we developed a spatially asymmetric nanoparticle, Fe3O4@DMS&PDA@MnO2-SRF, for enhanced ferroptosis. It consists of two subunits: Fe3O4 nanoparticles coated with dendritic mesoporous silica (DMS) and PDA@MnO2 (PDA: polydopamine) loaded sorafenib (SRF). The spatial isolation Fe3O4@DMS PDA@MnO2-SRF subunits enhances synergistic effect between GSH-scavengers ferroptosis-related components. First, increased exposure subunit Fenton reaction, leading to production reactive oxygen species. Furthermore, effectively depletes GSH, thereby inducing inactivation glutathione-dependent peroxidases 4. Moreover, SRF blocks Xc– transport augmenting GSH depletion capabilities. dual Fe3O4@DMS&PDA@MnO2-SRF significantly weakens antioxidative system, boosting chemodynamic performance cells.

Язык: Английский

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Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Язык: Английский

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Different Valence States of Copper Ion Delivery against Triple-Negative Breast Cancer

ACS Nano, Год журнала: 2024, Номер unknown

Опубликована: Фев. 6, 2024

Different valence states of copper (Cu) ions are involved in complicated redox reactions vivo, which closely related to tumor proliferation and death pathways, such as cuproptosis chemodynamic therapy (CDT). Cu ion mediated Fenton-like reagents induced cell presents compelling attention for the CDT tumors. However, superiority different antitumor effect is unknown. In this study, we investigated modulating by Cu-chelated cyanine dye against triple-negative breast cancer. The cuprous (Cu+) (Cu2+) were chelated with four nitrogen atoms dipicolylethylenediamine-modified construction Cu+ Cu2+ dyes (denoted CC1 CC2, respectively). Upon 660 nm laser irradiation, or CC2 can generate reactive oxygen species, could disrupt structure, achieving rapid release initiating reaction CDT. Compared Cu2+-based reagent, exhibited a better therapeutic outcome due there being no need reduction glutathione shorter route more hydroxyl radicals. Our findings suggest precision delivery achieve highly efficient therapy.

Язык: Английский

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Lipid Nanoparticular Codelivery System for Enhanced Antitumor Effects by Ferroptosis–Apoptosis Synergistic with Programmed Cell Death-Ligand 1 Downregulation

ACS Nano, Год журнала: 2024, Номер 18(26), С. 17267 - 17281

Опубликована: Июнь 13, 2024

Intrinsic or acquired resistance to chemical drugs severely limits their therapeutic efficacy in cancer treatment. Various intracellular antioxidant molecules, particularly glutathione (GSH), play a crucial role maintaining redox homeostasis by mitigating the overproduced reactive oxygen species (ROS) due rapid cell proliferation. Notably, these antioxidants also eliminate chemical-drug-induced ROS, eventually diminishing cytotoxicity and rendering them less effective. In this study, we combined erastin, GSH biosynthesis inhibitor, with 2'-deoxy-5-fluorouridine 5'-monophosphate sodium salt (FdUMP), an ROS-based drug, effectively disrupt reverse chemotherapy resistance. Therefore, efficient ferroptosis apoptosis were simultaneously induced for enhanced antitumor effects. Additionally, employed small interfering RNA targeting PD-L1 (siPD-L1) as third agent block immune-checkpoint recognition CD8

Язык: Английский

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