Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD‐L1 for Enhanced Cancer Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(22)

Published: March 14, 2023

Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces death. However, existing are small molecules with short blood half-life making it hard enough cells. Herein, reactive oxygen species (ROS)-sensitive polymer (PHPM) designed, used co-encapsulate elesclomol (ES) and form nanoparticles (NP@ESCu). After entering ES Cu, triggered by excessive intracellular ROS, readily released. work in concerted way not only kill cells cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu efficiently cuproptosis investigated. addition, change transcriptomes treated explored RNA-Seq. vivo, found mice model subcutaneous bladder cancer, reprograming tumor microenvironment. Additionally, further combined anti-programmed protein ligand-1 antibody (αPD-L1). This study provides first report combining nanomedicine can αPD-L1 for enhanced therapy, thereby providing novel strategy future therapy.

Language: Английский

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Aggregation‐induced emission luminogens for in vivo molecular imaging and theranostics in cancer

Aggregate, Journal Year: 2023, Volume and Issue: 4(5)

Published: May 6, 2023

Abstract Cancer is one of the most fatal diseases for decades. Aggregation‐induced emission luminogens (AIEgens) have been recently used as molecular imaging or therapeutic agents in cancers, due to advantages large Stokes shift, high quantum yield, great biocompatibility, and strong photostability. AIEgens can specifically target different types cancer via diverse targeting strategies. AIEgen‐based fluorescence imaging, especially near‐infrared demonstrated deep penetration suitable signal‐to‐noise ratio, which allows reliable vivo imaging. Combined with other modalities, multimodal could provide multidimensional hallmarks from perspectives. In addition, phototherapy be photodynamic therapy photothermal therapy, facilitate ablation cells good biosafety effects vivo. nanoparticles fabricated some specific chemicals, drugs, siRNA, display synergistic cancers. This paper comprehensively describes current status future perspectives AIEgens, showed a potential preclinical clinical translation on theranostics cancer.

Language: Английский

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Potential of Copper and Copper Compounds for Anticancer Applications

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(2), P. 234 - 234

Published: Feb. 3, 2023

Inducing cancer cell death has always been a research hotspot in life sciences. With the continuous deepening and diversification of related research, potential value metal elements inducing explored. Taking iron as an example, ferroptosis, mainly characterized by increasing load driving production large amounts lipid peroxides eventually leading to death, recently attracted great interest community. After iron, copper, trace element, received extensive attention especially tumor death. Copper its complexes can induce autophagy or apoptosis cells through variety different mechanisms action (activation stress pathways, arrest cycle, inhibition angiogenesis, cuproptosis, paraptosis), which are promising therapy have become new hotspots treatment research. This article reviews main applications novel copper compound-induced focusing on compounds their anticancer applications.

Language: Английский

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

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(8)

Published: Oct. 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

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

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(29)

Published: June 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

Language: Английский

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Copper homeostasis and cuproptosis in cancer immunity and therapy

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 211 - 227

Published: Sept. 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

Language: Английский

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The copper age in cancer treatment: From copper metabolism to cuproptosis

Progress in Materials Science, Journal Year: 2023, Volume and Issue: 138, P. 101145 - 101145

Published: May 23, 2023

Language: Английский

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Glutathione‐Scavenging Celastrol‐Cu Nanoparticles Induce Self‐Amplified Cuproptosis for Augmented Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(35)

Published: June 27, 2024

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis highly dependent on intracellular copper accumulation and counteracted by high level glutathione (GSH) in tumor cells. Here, this work develops self-amplified nanoparticles (Cel-Cu NP) using celastrol (Cel), natural product isolated from medical plant. In Cel-Cu NP, Cel serves as versatile ionophore, exhibiting an ideal coordination capacity toward ions without compromising the induction. Notably, can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, further activates immunogenic death (ICD) elicit robust immune response. Combining with checkpoint blockade, NP effectively eradicates metastatic tumors mouse lung metastasis model. This study provides efficient nanomedicine inducing for immunotherapy.

Language: Английский

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Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 6, 2024

Abstract Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with short blood half‐life, face challenges in transporting enough amounts ions into tumor cells. This work describes construction carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by coordination 2+ sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination cuproptosis and ferroptosis. Ce6@Cu NPs internalized U87MG cells induce sonodynamic effect glutathione (GSH) depletion capability, promoting lipid peroxidation eventually inducing Furthermore, + concentration increases as reacts reductive GSH, resulting downregulation ferredoxin‐1 lipoyl synthase. induces oligomerization lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress irreversible cuproptosis. possess satisfactory ability to penetrate blood‐brain barrier, significant accumulation orthotopic U87MG‐Luc glioblastoma. The ferroptosis evidenced both vitro vivo minimal side effects. represents promising therapeutic strategy combining cuproptosis, potentially inspiring further research developing logical effective cancer therapies based

Language: Английский

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