Mitochondria- and Anaerobic Glycolysis- Targeted Self-Assembled Copper Complex Nanoparticles for Boosting Cuproptosis- Immunotherapy DOI Creative Commons
Hanyu Zhang,

Jing Xia,

Lingling Xie

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Abstract Cuproptosis is an emerging regulated cell death that depends on the intracellular copper ion and mitochondrial respiration, showing great potential in cancer treatment. However, increasing specific accumulation of ions mitochondria while simultaneously enhancing respiration are highly needed still a major challenge to promote cuproptosis. Herein, lactate dehydrogenase (LDH) inhibitor galloflavin (GF) self-assembles with ionophore elesclomol (ES) through ion-driven cooperative coordination form GF/CuES nanoparticles, synergistically targeting anaerobic glycolysis boost cuproptosis-immunotherapy. After cellular internalization, nanoparticles responsively dissociate release Cu2+ ES, co-transporting into collaboratively trigger cuproptosis, which subsequently evokes immunogenic (ICD). Notably, liberated GF leads effective LDH suppression, not only further amplifies cuproptosis via disrupting but also reduces production, thus alleviating immunosuppressive tumor microenvironment augmenting anti-tumor immunity driven by ICD. Thus, exhibit strong antitumor effects cooperatively glycolysis, immunotherapy, offering unique opportunity enhance treatment strategies.

Language: Английский

Copper homeostasis and cuproptosis in health and disease DOI Creative Commons

Yunuo Yang,

Jiaxuan Wu,

Lisheng Wang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 17, 2024

Copper is a vital trace element in human physiology, essential for the synthesis of numerous crucial metabolic enzymes and facilitation various biological processes. Regulation copper levels within narrow range imperative maintaining homeostasis. Numerous studies have demonstrated significant roles homeostasis cuproptosis health disease pathogenesis. However, comprehensive up-to-date systematic review this domain remains absent. This aims to consolidate recent advancements understanding disease, focusing on underlying mechanisms potential therapeutic interventions. Dysregulation homeostasis, manifesting as either excess or deficiency, implicated etiology diseases. Cuproptosis, recently identified form cell death, characterized by intracellular overload. phenomenon mediates diverse array evolutionary processes organisms, spanning from genetic disorders, liver diseases, neurodegenerative cancers. provides summary pathogenic along with associated targeted agents. Furthermore, it explores future research directions yield treatment, management, prevention.

Language: Английский

Citations

9
Nanomaterial-enabled metabolic reprogramming strategies for boosting antitumor immunity DOI
Mengdi Ma, Yongliang Zhang, Kanyi Pu

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 2, 2024

We discuss the recent advances in nanomaterial design strategies for immunometabolic modulatory platforms and their applications targeting cancer-immunity cycle to enhance therapeutic outcomes.

Language: Английский

Citations

7
Copper-doped layered double hydroxides co-deliver proteins/drugs for cascaded chemodynamic/immunotherapy via dual regulation of tumor metabolism DOI
Gaoming Li, Zhi‐Qiang Wang, Yunqi Guo

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
Single-atom–doped piezocatalyst induces copper-free cuproptosis in tumor therapy DOI Creative Commons
M. Zhang, Xinran Song, Yu Qin

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(7)

Published: Feb. 14, 2025

Cuproptosis, a distinct cell death pathway, has been integrated into nanomedicine for disease theranostics. However, current nanosystems inducing cuproptosis rely on exogenous toxic copper ions, limiting the scope of biomaterials. Developing nanoplatforms that induce without holds substantial promise. Here, we engineered two-dimensional iron (Fe) single-atom–doped molybdenum disulfide (MoS 2 ) piezocatalyst (Fe-MoS tumor therapy. Incorporating single Fe atoms enhances MoS piezoelectric polarization via charge redistribution and modulates Mo oxidation states, enabling multifaceted enzymatic activities, including peroxidase-, glutathione oxidase–, oxidase-, catalase-like activities. Upon ultrasound stimulation, Fe-MoS nanocatalyst generates reactive oxygen species depletes synergistic piezocatalytic enzyocatalytic effects, disrupting ion homeostasis cuproptosis, concurrently triggering ferroptosis ferritinophagy, which collectively suppression. This study represents first paradigm to introduce copper-free initiating substantially advancing applications in

Language: Английский

Citations

1
Chiral nanoassembly remodels tumor microenvironment through non-oxygen-dependent depletion lactate for effective photodynamic immunotherapy DOI

Xuan Zhang,

Jinwei Bai, Shihao Sun

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 319, P. 123203 - 123203

Published: Feb. 21, 2025

Language: Английский

Citations

1
The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer DOI Creative Commons
Ziyu Guo,

Danyao Chen,

Lei Yao

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: May 8, 2025

Abstract Copper, an essential micronutrient, plays significant roles in numerous biological functions. Recent studies have identified imbalances copper homeostasis across various cancers, along with the emergence of cuproptosis, a novel copper-dependent form cell death that is crucial for tumor suppression and therapeutic resistance. As result, manipulating levels has garnered increasing interest as innovative approach to cancer therapy. In this review, we first delineate at both cellular systemic levels, clarifying copper’s protumorigenic antitumorigenic functions cancer. We then outline key milestones molecular mechanisms including mitochondria-dependent independent pathways. Next, explore cuproptosis biology, well interactions mediated by between cells immune system. also summarize emerging opportunities targeting discuss clinical associations cuproptosis-related genes. Finally, examine potential biomarkers put forward existing challenges future prospects leveraging Overall, review enhances our understanding landscape cancer, highlighting copper- or cuproptosis-based therapies treatment.

Language: Английский

Citations

1
Mitochondria- and anaerobic glycolysis-targeted self-assembled copper complex nanoparticles for boosting cuproptosis-immunotherapy DOI
Hanyu Zhang,

Jing Xia,

Lingling Xie

et al.

Advanced Composites and Hybrid Materials, Journal Year: 2024, Volume and Issue: 8(1)

Published: Dec. 16, 2024

Language: Английский

Citations

6
Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy DOI Creative Commons

Sai‐Nan Zhang,

Qibo Huang,

Tuo Ji

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Oct. 31, 2024

Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis critical human health, its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities metal ion regulation interact with fate. This review insights into the complex mechanisms metabolism, molecular basis cuproptosis, association cancer development. We assess role cuproptosis-related genes (CRGs) associated tumorigenesis, their importance prognostic indicators targets, impact on tumor microenvironment (TME) immune response. Ultimately, this highlights interplay between copper, immunotherapy.

Language: Английский

Citations

5
Quinoidal Semiconductor Nanoparticles for NIR‐II Photoacoustic Imaging and Photoimmunotherapy of Cancer DOI Open Access

Gaoli Niu,

Guangkun Song,

Yong Kang

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Photoagents with ultra-high near-infrared II (NIR-II) light energy conversion efficiency hold great promise in tumor phototherapy due to their ability penetrate deeper tissues and minimize damage surrounding healthy cells. However, the development of NIR-II photoagents remain challenging. In this study, an all-fused-ring quinoidal acceptor-donor-acceptor (A-D-A) molecule, SKCN, a BTP core is synthesized, nanoparticles named FA-SNPs are prepared. The unique structure enhances π-electron delocalization bond length uniformity, significantly reducing bandgap resulting strong absorption, high molar extinction coefficient, photothermal 75.14%. Enhanced molecular rigidity also facilitates efficient transfer oxygen, boosting reactive oxygen species generation. By incorporating immunomodulator R848, FA-SRNPs further developed, effectively modulating immune microenvironment by Tregs M-MDSCs infiltration, promoting dendritic cell maturation, M1 macrophage polarization, activating CD8+ T cells NK Comprehensive studies using orthotopic ovarian cancer models demonstrated targeting, photoacoustic imaging capabilities, significant suppression metastasis inhibition, showing excellent therapeutic efficacy breast model. This study provides evidence for potential application A-D-A molecules photoimmunotherapy.

Language: Английский

Citations

5
MOF-Derived Oxygen-Deficient Titania-Mediated Photodynamic/Photothermal-Enhanced Immunotherapy for Tumor Treatment DOI
Xin Jiang, Zhengjie Huang, Zhuqing Liu

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(27), P. 34591 - 34606

Published: June 25, 2024

Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy been largely limited by weak immune response and an immunosuppressive tumor microenvironment. Herein, we report metal–organic framework (MOF)-derived titanium oxide nanoparticle (MCTx NP) booster that can greatly improve the immunotherapy inducing "immunogenic cell death" (ICD) remodeling The NPs, inheriting characteristic structure of MIL-125 enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency reactive species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, NPs release O2 reduce glutathione (GSH) in environment, showcasing their potential to reverse In vitro/vivo results MCTx directly kill cells effectively eliminate primary tumors exerting dual photodynamic/photothermal therapy under single NIR irritation. At same time, augment PD-L1 blockade potently ICDs reversing microenvironment, including promoting dendritic (DC) maturation, decreasing regulatory T (Tregs)' infiltration, increasing cytotoxic lymphocytes (CTLs) helper (Ths), resulting effective distant suppression. This work highlights NP-mediated photodynamic- photothermal-enhanced strategy treatment.

Language: Английский

Citations

4