Bioorthogonal Cu Single‐atom Nanozyme for Synergistic Nanocatalytic Therapy, Photothermal Therapy, Cuproptosis, and Immunotherapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(27)

Published: April 24, 2024

Single-atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in-depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis sputtered SAzymes by in situ bombarding-embedding technique. Using this method, copper (Cu) (CuSA) is developed unreported unique planar Cu-C

Language: Английский

---

Protein lipoylation: mitochondria, cuproptosis, and beyond

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(8), P. 729 - 744

Published: May 6, 2024

Language: Английский

---

Cuproptosis and Cu: a new paradigm in cellular death and their role in non-cancerous diseases

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(9-10), P. 1330 - 1360

Published: July 16, 2024

Language: Английский

---

MAMMALIAN COPPER HOMEOSTASIS: PHYSIOLOGIC ROLES AND MOLECULAR MECHANISMS

Physiological Reviews, Journal Year: 2024, Volume and Issue: 105(1), P. 441 - 491

Published: Aug. 22, 2024

In the past decade, evidence for numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries Cu involvement cell signaling, autophagy, motility, differentiation, and regulated death (cuproptosis) have markedly extended list already known functions Cu, such as a cofactor essential metabolic enzymes, protein structural component, regulator trafficking. Novel unexpected transporting proteins enzymes been identified, new disorders homeostasis described. Significant progress made mechanistic studies two classic metabolism, Menkes disease Wilson’s disease, which paved way novel approaches to their treatment. discovery cuproptosis role metastatic growth increased interest targeting homeostatic pathways treat cancer. this review, we summarize established concepts field discuss how decade expand modify these concepts. brain metabolism functional speciation recently discovered attracted significant attention are highlighted review.

Language: Английский

---

Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits

Antioxidants, Journal Year: 2024, Volume and Issue: 13(10), P. 1228 - 1228

Published: Oct. 12, 2024

Alpha-lipoic acid (ALA) is a bioactive molecule with significant health effects. The biological action of ALA has been ascribed to the characteristic antioxidant properties oxidized form and its reduced counterpart dihydrolipoic (DHLA) system. ALA/DHLA combination represents an ideal since it can quench radicals, able chelate metals, amphiphilic, no major adverse This unique system scavenge reactive oxygen species, exerting effect on tissue levels forms other antioxidants, including glutathione. For this reason, also known as "antioxidant antioxidants". review analyzes antioxidant, anti-inflammatory, neuroprotective effects discusses applications ameliorative tool for chronic diseases those associated oxidative stress. Results from in vitro vivo studies demonstrated that modulates various stress pathways suggesting application, alone or functional substances, useful support numerous conditions, which balance oxidant-antioxidant disrupted, such neurodegenerative disorders. Based several successful clinical studies, established oral supplements are clinically relieving complications diabetes disorders cardiovascular nerve discomforts be considered approach improving our health.

Language: Английский

---

Post-traumatic stress disorder, diabetes mellitus, and alpha-lipoic acid

INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), Journal Year: 2025, Volume and Issue: 21(1), P. 82 - 94

Published: Feb. 23, 2025

Post-traumatic stress disorder (PTSD) is a prognostic factor for the development of metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), increases risk cardiometabolic pathologies and neurodegenerative diseases. At same time, T2DM MetS can also cause major neurosis-like psychiatric symptoms characteristic PTSD. Their influence manifested through negative effects on central nervous system, in particular Oxidative chronic low-grade inflammation play an important role pathophysiology PTSD, MetS, T2DM, making them main therapeutic targets. Targeted oxidative stress, mitochondrial metabolism disorders, use antioxidants, α-lipoic acid (ALA), positively affect not only course comorbidities but manifestations In vitro vivo studies have demonstrated that ALA modulates number pathways associated with stress. addition, results clinical trials confirm antioxidant mechanism action patients obesity, 1 2. The neuroprotective activity being actively studied proving promising as approach treatment PTSD Despite significant potential ALA, its application limited by several barriers. particular, lack standardized protocols, well detailed assessment effectiveness alone. pharmacokinetic profile remains limited, which one factors hinder use. this context, there are certain prospects transportation systems based nanoparticles, potentially solve these problems. technologies so­lid lipid nanoparticles such niosomes, liposomes, nanostructured carriers micelles provide possibility local or systemic ALA. However, further preclinical needed to definitively determine feasibility search was conducted Scopus, Science Direct (from Elsevier) PubMed, including MEDLINE databases. keywords used were “α-lipoic acid”, “post-traumatic disorder”, “diabetes mellitus”, “metabolic syndrome”. A manual bibliography publications identify study could be found during online search.

Language: Английский

---

α-lipoic acid ameliorates consequences of copper overload by up-regulating selenoproteins and decreasing redox misbalance

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(40)

Published: Sept. 26, 2023

α-lipoic acid (LA) is an essential cofactor for mitochondrial dehydrogenases and required cell growth, metabolic fuel production, antioxidant defense. In vitro, LA binds copper (Cu) with high affinity as endogenous membrane permeable metabolite could be advantageous in mitigating the consequences of Cu overload human diseases. We tested this hypothesis 3T3-L1 preadipocytes inactivated transporter Atp7a; these cells accumulate show morphologic changes mitochondria impairment. Treatment corrected morphology Atp7a −/− similar to chelator bathocuproinedisulfonate (BCS) improved function; however, mechanisms BCS action were different. Unlike BCS, did not decrease intracellular but instead increased selenium levels that low cells. Proteome analysis confirmed distinct responses compounds identified upregulation selenoproteins major effect on preadipocytes. Upregulation was associated GSH:GSSG ratio cellular compartments, which lowered by elevated Cu, reversal protein oxidation. Thus, diminishes toxic effects improving redox environment. also are decreased tissues a Wilson disease animal model, especially liver, making attractive candidate supplemental treatment disease.

Language: Английский

---

Bioorthogonal Cu Single‐Atom Nanozyme for Synergistic Nanocatalytic Therapy, Photothermal Therapy, Cuproptosis and Immunotherapy

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(27)

Published: April 24, 2024

Abstract Single‐atom nanozymes (SAzymes) with atomically dispersed active sites are potential substitutes for natural enzymes. A systematic study of its multiple functions can in‐depth understand SAzymes's nature, which remains elusive. Here, we develop a novel ultrafast synthesis sputtered SAzymes by in situ bombarding‐embedding technique. Using this method, copper (Cu) (CuSA) is developed unreported unique planar Cu‐C 3 coordinated configuration. To enhance the tumor‐specific targeting, employ bioorthogonal approach to engineer CuSA, denoted as CuSACO. CuSACO not only exhibits minimal off‐target toxicity but also possesses exceptional ultrahigh catalase‐, oxidase‐, peroxidase‐like multienzyme activities, resulting reactive oxygen species (ROS) storm generation effective tumor destruction. Surprisingly, release Cu ions presence glutathione (GSH) induce cuproptosis, enhancing treatment efficacy. Notably, CuSACO′s remarkable photothermal properties enables precise therapy (PTT) on tumors. This, combined nanozyme catalytic cuproptosis and immunotherapy, efficiently inhibiting growth orthotopic breast tumors gliomas, lung metastasis. Our research highlights an innovative strategy utilize mechanism therapeutic efficacy, broadening exploration development enzyme‐like behavior physiological action SAzymes.

Language: Английский

---

ATP7A-dependent copper sequestration contributes to termination of β-CATENIN signaling during early adipogenesis

Molecular Metabolism, Journal Year: 2024, Volume and Issue: 80, P. 101872 - 101872

Published: Jan. 6, 2024

Adipocyte fate determination is tightly regulated by extrinsic signaling pathways and intrinsic metabolic morphologic changes that maintain adipose tissue function. Copper (Cu) homeostasis required for the normal metabolism of mature adipocytes, whereas role Cu in adipogenesis unclear To determine adipocytes differentiation, we used 3T3-L1 immunocytochemistry, X-ray fluorescence, mass-spectrometry, pharmacological treatments, manipulations copper levels In differentiating cells, adipogenic stimuli trigger upregulation trafficking transporter Atp7a, thus causing redistribution from cytosol to vesicles. Disrupting deletion Atp7a results elevation inhibition adipogenesis. The C/EBPβ, an initial step adipogenesis, not affected Atp7a-/- subsequent PPARγ inhibited. Comparison wild type proteomes during early differentiation revealed stabilization β-catenin, a negative regulator chelation, or overexpression Atp7b restored β-catenin down-regulation intracellular targeting buffering contributes termination signaling. Abnormal was also observed vivo livers Atp7b-/- mice, which accumulate Cu, suggesting tissue-independent crosstalk between Wnt/β-catenin pathway. These point new regulatory contribute better understanding human disorders misbalance.

Language: Английский

---

Nanoparticle‐Driven Skeletal Muscle Repair and Regeneration Through Macrophage‐Muscle Stem Cell Interaction

Small, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Macrophages are key innate immune cells in the muscle environment of sarcopenia patients, significantly influencing stem cell (MuSC) proliferation and differentiation. However, prolonged activation macrophages can hinder recovery. In this study, it synthesizes lipoic acid-modified gold nanoparticles (LA-Au NPs) varying sizes to evaluate their biocompatibility immunomodulatory effects. The findings demonstrate that LA-Au NPs exhibit excellent with promoted M2 polarization a size-dependent manner. Mechanistically, facilitated metabolic reprogramming by enhancing lysosomal autophagy mitochondrial oxidative phosphorylation. Furthermore, shown chemotax toward MuSCs, regulating via chemokine system, inhibiting MuSC apoptosis, differentiation under inflammatory conditions. vivo studies have confirmed safety efficacy mice. To further enhance effectiveness NPs, investigates delivery strategy involves preconditioning (Mac@Au NPs). Compared direct injection Mac@Au greater benefits for repair. This highlights potential macrophage therapy as promising effective regeneration therapeutic intervention sarcopenia.

Language: Английский

---