Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Oct. 9, 2023

Abstract The use of nanotechnology has the potential to revolutionize detection and treatment cancer. Developments in protein engineering materials science have led emergence new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers medicinal purposes been approved human trials, only a few authorized clinical cells. In this review, we analyze some formulations discuss challenges translating findings from lab clinic. This study highlights various compounds that can be used selective tumor inherent difficulties therapy. Nanotechnology provides promising platform improving future, but further research is needed overcome current limitations translation. Graphical

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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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, Journal Year: 2024, Volume and Issue: 146(6), P. 3675 - 3688

Published: Feb. 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.

Language: Английский

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Engineered Living Materials for Advanced Diseases Therapy

Advanced Materials, Journal Year: 2023, Volume and Issue: unknown

Published: July 12, 2023

Abstract Natural living materials serving as biotherapeutics exhibit great potential for treating various diseases owing to their immunoactivity, tissue targeting, and other biological activities. In this review, the recent developments in engineered materials, including mammalian cells, bacteria, viruses, fungi, microalgae, plants, active derivatives that are used summarized. Further, future perspectives challenges of such material‐based discussed provide considerations advances biomedical applications.

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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Delivering metal ions by nanomaterials: Turning metal ions into drug-like cancer theranostic agents

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 494, P. 215332 - 215332

Published: July 17, 2023

Language: Английский

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Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116115 - 116115

Published: Jan. 5, 2024

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.

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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Stimulus‐Responsive Copper Complex Nanoparticles Induce Cuproptosis for Augmented Cancer Immunotherapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 25, 2024

Abstract Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy cuproptosis remains limited by poor delivery efficiency copper ion carriers. Herein, complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver into cells to induce cuproptosis. NP demonstrate stimulus‐responsive release complexes, which results mitochondrial dysfunction and promotes aggregation lipoylated dihydrolipoamide S‐acetyltransferase (DLAT), leading Notably, not only cuproptosis, but also elicit robust immune responses suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis‐based

Language: Английский

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