Enhanced Bacterial Cuproptosis‐Like Death via Reversal of Hypoxia Microenvironment for Biofilm Infection Treatment

Advanced Science, Journal Year: 2024, Volume and Issue: 11(19)

Published: March 13, 2024

Abstract A recently emerging cell death pathway, known as copper‐induced death, has demonstrated significant potential for treating infections. Existing research suggests that cells utilizing aerobic respiration, opposed to those reliant on glycolysis, exhibit greater sensitivity death. Herein, a MnO 2 ‐loaded copper metal–organic frameworks platform is developed denoted MCM, enhance bacterial cuproptosis‐like via the remodeling of respiratory metabolism. The reversal hypoxic microenvironments induced cascade responses, encompassing reactivation suppressed immune responses and promotion osteogenesis angiogenesis. Initially, MCM catalyzed O production, alleviating hypoxia within biofilm inducing transition in respiration mode from glycolysis respiration. Subsequently, sensitized bacteria, characterized by enhanced tricarboxylic acid cycle activity, underwent owing increased concentrations aggregated intracellular dihydrolipoamide S‐acetyltransferase (DLAT). disruption also stimulated dendritic macrophages, thereby strengthening their antimicrobial activity through chemotaxis phagocytosis. Moreover, nutritional effects elements, coupled with alleviation, synergistically facilitated regeneration bones blood vessels. Overall, reshaping infection microenvironment presents promising avenue eradicating biofilms.

Language: Английский

---

Mucous Permeable Nanoparticle for Inducing Cuproptosis‐Like Death In Broad‐Spectrum Bacteria for Nebulized Treatment of Acute Pneumonia

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract The emergence of antibiotic‐resistant bacteria has exacerbated the challenge treating infectious diseases. Quorum sensing (QS), a bacterial communication system regulating virulence and biofilm formation, presents target for novel therapies. Cuproptosis death is innovation mode death, however, this effect may be partially inhibited by glutathione (GSH). Buthionine sulfoximine (BSO) responsible GSH biosynthesis been identified as potential promoter cuproptosis death. Here, Cu 2 O‐BSO NPs with lung adhesion mucus penetration ability are synthesized incorporating BSO onto O, modifying it DOPA PEG. demonstrated broad‐spectrum antibacterial activity against both Gram‐positive Gram‐negative bacteria, making viable treatment option MRSA‐induced acute pneumonia. Specifically, can synergistically enhance cuproptosis‐like hinder QS system, eradicate biofilms, reduce strains, stimulate chemotaxis phagocytosis macrophages, ultimately improve in mice severe This research wide‐ranging alternative, providing promise addressing microbial resistance combatting formation. Additionally, established theoretical foundation clinical numerous challenging cases drug‐resistant bacteria.

Language: Английский

---

Oxygen-supplying nanotherapeutics for bacterial septic arthritis via hypoxia-relief-enhanced antimicrobial and anti-inflammatory phototherapy

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 1043 - 1057

Published: Feb. 24, 2025

Language: Английский

---

Ultrasound-Activated Piezoelectric Heterojunction Drives Nanozyme Catalysis to Induce Bacterial Cuproptosis-Like Death and Promote Bone Vascularization and Osseointegration

Biomaterials, Journal Year: 2025, Volume and Issue: 320, P. 123249 - 123249

Published: March 6, 2025

Language: Английский

---

A Mucous Permeable Local Delivery Strategy Based on Manganese-Enhanced Bacterial Cuproptosis-like Death for Bacterial Pneumonia Treatment

ACS Nano, Journal Year: 2024, Volume and Issue: 18(46), P. 31923 - 31940

Published: Nov. 7, 2024

Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering antibiotic abuse resistance bacterial biofilms, a variety metal-based materials have been developed. However, due to oxygen environment lungs, some aerobic infection bacteria tolerance ROS, based on ROS may not achieve good therapeutic effects. Inspired by sensitivity cuproptosis respiratory cells, we designed copper composite antibacterial nanoparticle found that it can effectively induce cuproptosis-like death in lungs. To address challenge

Language: Английский

---

The Role of Ferroptosis and Cuproptosis in Tuberculosis Pathogenesis: Implications for Therapeutic Strategies

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 99 - 99

Published: Feb. 5, 2025

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) remains a global health crisis, with over 10 million people affected annually. Despite advancements in treatment, M.tb has developed mechanisms to evade host immune responses, complicating efforts eradicate the disease. Two emerging cell death pathways, ferroptosis and cuproptosis, have been linked TB pathogenesis. Ferroptosis, an iron-dependent form of death, is driven lipid peroxidation reactive oxygen species (ROS) accumulation. This process can limit replication depleting intracellular iron inducing macrophage necrosis. However, excessive may lead tissue damage aid bacterial dissemination. Cuproptosis, triggered copper accumulation, disrupts mitochondrial metabolism, leading protein aggregation death. exploits both metabolism survive within macrophages, manipulating these processes resist oxidative stress responses. review examines roles cuproptosis TB, discussing how manipulates pathways for survival. While therapeutic strategies targeting processes, such as inducers (Erastin, RSL3) inhibitors (Ferrostatin-1) ionophores (Disulfiram, Elesclomol) chelators, show promise, limited understanding potential off-target effects significant challenge. Further exploration provide insights into development targeted therapies aimed at controlling infection while minimizing damage. By elucidating complex interactions between ferroptosis, future could better address resistance improve clinical outcomes.

Language: Английский

---

Biodegradable Janus sonozyme with continuous reactive oxygen species regulation for treating infected critical-sized bone defects

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 3, 2024

Critical-sized bone defects are usually accompanied by bacterial infection leading to inflammation and nonunion. However, existing biodegradable materials lack long-term therapeutical effect because of their gradual degradation. Here, a degradable material with continuous ROS modulation is proposed, defined as sonozyme due its functions sonosensitizer nanoenzyme. Before degradation, the can exert an effective sonodynamic antimicrobial through dual active sites MnN4 Cu2O8. Furthermore, it promote anti-inflammation superoxide dismutase- catalase-like activities. Following quercetin-metal chelation exhibits sustaining antioxidant ligand-metal charge transfer, while released ions quercetin also have great self-antimicrobial, osteogenic, angiogenic effects. A rat model infected cranial demonstrates rapidly eliminate bacteria regeneration. This work presents promising approach engineer long-time effects for infectious defects. Existing authors develop modulation, which eliminates promotes regeneration in

Language: Английский

---

Copper‐infused zinc porphyrin supramolecular polymersomes for triple synergistic combat against wound bacterial biofilm infections

Aggregate, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Bacterial biofilm infections (BBI) on wound surfaces and implants pose a significant clinical challenge due to the impermeable nature of biofilms obstacles in tissue repair. Traditional photothermal therapy (PTT) or chemodynamic (CDT), whether used alone combination, often causes damage surrounding normal tissues from high operating temperatures elevated levels reactive oxygen species, leading unsatisfactory anti‐biofilm effects. This study introduces novel copper ions loaded zinc porphyrin polymer vesicle (Cu‐PPS) that employs triple synergistic approach involving PTT, CDT, bacterial cuproptosis‐like death (BCD). Cu‐PPS exhibits exceptional efficiency 51.06%, promoting release under stimulation, enhancing CDT BCD effectiveness, facilitating mature clearance achieves bactericidal rate exceeding 99% an 93.32% vitro also excellent efficacy treating BBI vivo. presents innovative therapeutic strategy for combating infections, addressing challenges encountered management BBI.

Language: Английский

---

Synergistic enhancement of low-dose radiation therapy via cuproptosis and metabolic reprogramming for radiosensitization in in situ hepatocellular carcinoma

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 19, 2024

Radiotherapy (RT) is a primary clinical approach for cancer treatment, but its efficacy often hindered by various challenges, especially radiation resistance, which greatly compromises the therapeutic effectiveness of RT. Mitochondria, central to cellular energy metabolism and regulation cell death, play critical role in mechanisms radioresistance. In this context, cuproptosis, novel copper-induced mitochondria-respiratory-dependent death pathway, offers promising avenue radiosensitization. study, an innovative theranostic nanoplatform was designed induce cuproptosis synergy with low-dose therapy (LDRT, i.e., 0.5–2 Gy) treatment situ hepatocellular carcinoma (HCC). This aims reverse hypoxic tumor microenvironment, promoting shift from glycolysis oxidative phosphorylation (OXPHOS), thereby enhancing sensitivity cuproptosis. Concurrently, Fenton-like reaction ensures sustained supply copper depletion glutathione (GSH), inducing disrupting mitochondrial function, interrupting supply. strategy effectively overcomes radioresistance enhances against tumors. conclusion, study elucidates intricate interactions among hypoxia reversal, metabolic reprogramming, radiosensitization, particularly context treating carcinoma, providing paradigm radiotherapy.

Language: Английский

---

Pd/Ag2S with GSHOx-mimetic activity for anti-infections by amplifying photodynamic effects

Materials Letters, Journal Year: 2024, Volume and Issue: 371, P. 136874 - 136874

Published: Sept. 1, 2024

Language: Английский

---