Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Апрель 2, 2024

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.

Язык: Английский

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Ferroptosis inducers enhanced cuproptosis induced by copper ionophores in primary liver cancer

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Июнь 6, 2023

Cuproptosis and ferroptosis are the two newly defined metal-related regulated cell death. However, crosstalk between cuproptosis is obscure.We analyzed effect of inducers on copper ionophores-induced death through CCK-8 assay. was studied using immunofluorescence protein soluble-insoluble fraction isolation. GSH assay, qRT-PCR western blot were adopted to explore machinery enhanced cuproptosis. And mouse xenograft model built detect synergy elesclomol-Cu sorafenib in vivo.Herein we found that erastin could enhance primary liver cancer cells by increasing dependent lipoylated aggregation. Mechanically, upregulated lipoylation via suppressing mitochondrial matrix-related proteases mediated ferredoxin 1 (FDX1) degradation, reduced intracellular chelator glutathione (GSH) synthesis inhibiting cystine importing.Our findings proposed combination ionophores co-targeting be a novel therapeutic strategy for cancer.

Язык: Английский

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Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Год журнала: 2023, Номер 36(8)

Опубликована: Окт. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Язык: Английский

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Multifaceted Carbonized Metal–Organic Frameworks Synergize with Immune Checkpoint Inhibitors for Precision and Augmented Cuproptosis Cancer Therapy

ACS Nano, Год журнала: 2024, Номер 18(27), С. 17852 - 17868

Опубликована: Июнь 28, 2024

The discovery of cuproptosis, a copper-dependent mechanism programmed cell death, has provided way for cancer treatment. However, cuproptosis inherent limitations, including potential cellular harm, the lack targeting, and insufficient efficacy as standalone Therefore, exogenously controlled combination treatments have emerged key strategies cuproptosis-based oncotherapy. In this study, Cu2–xSe@cMOF nanoplatform was constructed combined sonodynamic/cuproptosis/gas therapy. This platform enabled precise cotreatment, with external control allowing selective induction in cells. approach effectively prevented metastasis recurrence. Furthermore, antiprogrammed death protein ligand-1 antibody (aPD-L1), maximized advantages immune checkpoint Additionally, under ultrasound irradiation, H2Se gas generated from induced cytotoxicity Further, it reactive oxygen species, which hindered survival proliferation. study reports an externally system that combines carbonized metal–organic framework aPD-L1 to enhance precision reinforced therapy could be valuable effective therapeutic agent reduce mortality morbidity future.

Язык: Английский

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Redox Homeostasis Disruptors Based on Metal‐Phenolic Network Nanoparticles for Chemo/Chemodynamic Synergistic Tumor Therapy through Activating Apoptosis and Cuproptosis

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(29)

Опубликована: Июнь 27, 2023

The combination of chemo/chemodynamic therapy is a promising strategy for improving antitumor efficacy. Herein, metal-phenolic network nanoparticles (NPs) self-assembled from copper ions and gallic acid (Cu-GA) are developed to evoke apoptosis cuproptosis synergistic therapy. Cu-GA NPs biodegraded in response the highly expressed glutathione (GSH) tumor cells, resulting simultaneous release Cu+ GA. intracellular GSH content dramatically reduced by released GA, rendering cells incapable scavenging reactive oxygen species (ROS) more susceptible cuproptosis. Meanwhile, ROS levels within significantly increased Fenton-like reaction , which disrupts redox homeostasis achieves apoptosis-related chemodynamic Moreover, massive accumulation further induces aggregation lipoylated dihydrolipoamide S-acetyltransferase downregulation iron-sulfur cluster protein, activating enhance efficacy NPs. experiments vivo demonstrate that exhibited excellent biosafety superior capacity, can efficiently inhibit growth tumors due activation specific hydrogen peroxide. These Cu-based provide potential build up efficient safe cancer

Язык: Английский

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Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

Advanced Science, Год журнала: 2024, Номер 11(18)

Опубликована: Март 2, 2024

Abstract The induction of cuproptosis, a recently identified form copper‐dependent immunogenic cell death, is promising approach for antitumor therapy. However, sufficient accumulation intracellular copper ions (Cu 2+ ) in tumor cells essential inducing cuproptosis. Herein, an intelligent cuproptosis‐inducing nanosystem constructed by encapsulating oxide (CuO) nanoparticles with the ionophore elesclomol (ES). After uptake cells, ES@CuO degraded to release Cu and ES synergistically trigger thereby significantly inhibiting growth murine B16 melanoma cells. Moreover, further promoted cuproptosis‐mediated immune responses reprogrammed immunosuppressive microenvironment increasing number tumor‐infiltrating lymphocytes secreted inflammatory cytokines. Additionally, combining programmed death‐1 (PD‐1) immunotherapy substantially increased efficacy melanoma. Overall, findings this study can lead use novel strategy therapy, which may enhance checkpoint inhibitor

Язык: Английский

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Copper in cancer: from limiting nutrient to therapeutic target

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Июнь 23, 2023

As an essential nutrient, copper’s redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity treat copper-sensitive may offer new strategies for specific disease treatments. In particular, concentration is typically higher in cancer cells, making a critical limiting nutrient cell growth proliferation. Hence, intervening metabolism cells become potential tumor treatment strategy, directly impacting metastasis. this review, we discuss body summarize research progress on role promoting inducing programmed death Additionally, elucidate copper-related drugs treatment, intending provide perspectives treatment.

Язык: Английский

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Single-Site Nanozymes with a Highly Conjugated Coordination Structure for Antitumor Immunotherapy via Cuproptosis and Cascade-Enhanced T Lymphocyte Activity

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(6), С. 3675 - 3688

Опубликована: Фев. 2, 2024

The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor cells impede infiltration killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) lysyl inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. conjugated organic ligand well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 H2O2 ·O2– ·OH. This surge reactive oxygen species (ROS) leads impaired mitochondrial function insufficient ATP supply, impacting copper-transporting ATPase-1 causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms glutathione peroxidase 4 depletion also induce lipid peroxidation trigger ferroptosis. Simultaneously, ROS-triggered release LOX-IN-3 reshapes ECM by inhibiting activity further enhances cytotoxic lymphocytes (CD8+ cells). CHO-triggered not only increases ·OH generation but downregulates expression ICs such as PD-1 TIM-3, restoring tumor-infiltrating CD8+ cells. Therefore, Cu-DBCO/CL exhibits efficient properties activating potent response cascade-enhanced cell viability. More importantly, remodeling could suppress metastasis proliferation In short, this nanoremodeler can greatly enhance enhancing immunogenicity, ECM, downregulating ICs, thus achieving effective inhibition growth metastasis.

Язык: Английский

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Copper homeostasis and cuproptosis in cancer immunity and therapy

Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 211 - 227

Опубликована: Сен. 16, 2023

Summary Copper is an essential nutrient for maintaining enzyme activity and transcription factor function. Excess copper results in the aggregation of lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), which correlates to mitochondrial tricarboxylic acid (TCA) cycle, resulting proteotoxic stress eliciting a novel cell death modality: cuproptosis. Cuproptosis exerts indispensable role cancer progression, considered promising strategy therapy. Cancer immunotherapy has gained extensive attention owing breakthroughs immune checkpoint blockade; furthermore, cuproptosis strongly connected modulation antitumor immunity. Thus, thorough recognition concerning mechanisms involved metabolism may facilitate improvement management. This review outlines cellular molecular characteristics links regulated modality with human cancers. We also current knowledge on complex effects immunity response. Furthermore, potential agents that elicit pathways are summarized. Lastly, we discuss influence induction tumor microenvironment as well challenges adding regulators therapeutic strategies beyond traditional

Язык: Английский

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Nanoparticles Synergize Ferroptosis and Cuproptosis to Potentiate Cancer Immunotherapy

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

Опубликована: Март 13, 2024

Abstract The recent discovery of copper‐mediated and mitochondrion‐dependent cuproptosis has aroused strong interest in harnessing this novel mechanism cell death for cancer therapy. Here the design a core‐shell nanoparticle, CuP/Er, co‐delivery copper (Cu) erastin (Er) to cells synergistic ferroptosis is reported. anti‐Warburg effect Er sensitizes tumor Cu‐mediated cuproptosis, leading irreparable mitochondrial damage by depleting glutathione enhancing lipid peroxidation. CuP/Er induces immunogenic death, enhances antigen presentation, upregulates programmed death‐ligand 1 expression. Consequently, promotes proliferation infiltration T cells, when combined with immune checkpoint blockade, effectively reinvigorates mediate regression murine colon adenocarcinoma triple‐negative breast prevent metastasis. This study suggests unique opportunity synergize combination therapy nanoparticles elicit antitumor effects potentiate current immunotherapies.

Язык: Английский

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