An Immunoregulation Hydrogel with Controlled Hyperthermia‐Augmented Oxygenation and ROS Scavenging for Treating Diabetic Foot Ulcers

Advanced Functional Materials, Год журнала: 2024, Номер 34(33)

Опубликована: Май 6, 2024

Abstract Diabetic foot ulcers (DFUs), a serious and increasingly common chronic issue among diabetics, often do not respond well to generalized treatment strategies. Hypoxia the overexpression of reactive oxygen species (ROS), resulting in inflammatory dysregulation subsequent imbalance macrophage phenotypes, are critical factors contributing prolonged non‐healing DFU wounds. These two issues interact continuous, problematic cycle. Presently, there is lack comprehensive strategies aimed at addressing both these simultaneously interrupt this detrimental Herein, an immunomodulatory hydrogel (PHG2) developed for reshaping hostile microenvironment. The engineered PHG2 only removes excess internally‐produced ROS but also generates O 2 , with its efficiency further boosted by local hyperthermia (42.5 °C) activated near‐infrared light. Through vitro vivo studies, along transcriptomic assessment, it confirmed that disrupts feedback loop between inflammation while lowering M1/M2 ratio. Such discoveries contribute significant enhancement healing process injuries undergo gradual increase movement, covering wounds from back, mouth, foot. Ultimately, method provides easy, safe, highly effective solution treating DFUs.

Язык: Английский

---

CuCo₂O₄ Nanoflowers with Multiple Enzyme Activities for Treating Bacterium-Infected Wounds via Cuproptosis-like Death

ACS Nano, Год журнала: 2024, Номер 18(24), С. 15845 - 15863

Опубликована: Июнь 4, 2024

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited efficiency of nanozyme-based materials often restrict effectiveness wound infection treatment. In this study, CuCo2O4 nanoflowers with multiple enzymatic activities were prepared antibacterial/antibiofilm by cuproptosis-like death. exhibited peroxidase-like (POD-like) oxidase-like (OXD-like) dual enzyme that generated large amounts •OH O2•–. Moreover, glutathione (GSH-Px-like) activity was able to reduce overexpression GSH in microenvironment, enhancing therapeutic effects reactive oxygen species (ROS). The morphology modified using hydrothermal method PEG4000 as solvent, resulting exposure more active center sites significant improvement activity. vitro results demonstrated pronounced disruption effect on biofilms formed bacteria. vivo, significantly promoted angiogenesis, collagen deposition, cell proliferation. Transcriptome sequencing revealed elevated ROS levels bacteria led membrane damage metabolic disruption. addition, Cu2+ overload induces lipid peroxidation accumulation disrupts respiratory chain tricarboxylic acid (TCA) cycle, ultimately leading This strategy, which combines synergistic enzyme-like death, an approach treating biofilm infections.

Язык: Английский

---

Ultrasound-activated piezo-hot carriers trigger tandem catalysis coordinating cuproptosis-like bacterial death against implant infections

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 22, 2024

Abstract Implant-associated infections due to the formation of bacterial biofilms pose a serious threat in medical healthcare, which needs effective therapeutic methods. Here, we propose multifunctional nanoreactor by spatiotemporal ultrasound-driven tandem catalysis amplify efficacy sonodynamic and chemodynamic therapy. By combining piezoelectric barium titanate with polydopamine copper, ultrasound-activated piezo-hot carriers transfer easily copper polydopamine. It boosts reactive oxygen species production piezoelectrics, facilitates interconversion between Cu2 + Cu promote hydroxyl radical generation via -catalyzed reactions. Finally, elevated cause membrane structure loosening DNA damage. Transcriptomics metabolomics analysis reveal that intracellular overload restricts tricarboxylic acid cycle, promoting cuproptosis-like death. Therefore, polyetherketoneketone scaffold engineered designed shows excellent antibacterial performance ultrasound stimulation promotes angiogenesis osteogenesis on-demand vivo.

Язык: Английский

---

Reactive Oxygen Species Responsive Nitric Oxide Release for Enhanced Photodynamic Antibacterial Therapy of Scaffolds

ACS Applied Polymer Materials, Год журнала: 2024, Номер 6(11), С. 6581 - 6593

Опубликована: Май 24, 2024

Photodynamic therapy (PDT) presented tremendous potential for combating implant-related infections, but its antibacterial efficacy was constrained by rapid electron–hole pair recombination of photosensitizers and barrier action a dense biofilm on reactive oxygen species (ROS). Herein, cascade phototherapeutic AuKN-LA nanosystem constructed depositing Au nanoparticles l-arginine (LA) potassium niobate (KN) photosensitizer. In the nanosystem, with lower Fermi levels could capture photogenerated electrons thus suppress to enhance ROS generation. Especifically, trigger generated release nitric oxide (NO) destroy biofilm, thereby facilitating entry ROS. Furthermore, NO itself possessed activity, which form synergy PDT. Then, introduced into poly(l-lactic acid) scaffolds fabricated laser additive manufacturing. Photoelectrochemical analysis proved that separation improved, significantly increasing detection crystal violet staining showed effectively remove sustainably releasing under light irradiation. As consequence, exhibited excellent rates 98.7% 99.2% against E. coli S. aureus, respectively, disrupting bacterial cell membranes causing leakage nucleic acid molecules proteins.

Язык: Английский

---

Nanoarchitectonics of in Situ Antibiotic-Releasing Acicular Nanozymes for Targeting and Inducing Cuproptosis-like Death to Eliminate Drug-Resistant Bacteria

ACS Nano, Год журнала: 2024, Номер 18(35), С. 24327 - 24349

Опубликована: Авг. 22, 2024

A series of progress has been made in the field antimicrobial use nanozymes due to their superior stability and decreased susceptibility drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) complex wound environments low targeting ability catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach bacteria; these exhibit OXD-like GSH-px-like dual enzyme activities produce ROS induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results

Язык: Английский

---

Bioinspired soft-hard combined system with mild photothermal therapeutic activity promotes diabetic bone defect healing via synergetic effects of immune activation and angiogenesis

Theranostics, Год журнала: 2024, Номер 14(10), С. 4014 - 4057

Опубликована: Янв. 1, 2024

Background:The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced homeostasis.Thus, an advanced multifunctional therapeutic platform capable simultaneously achieving immune regulation, elimination, tissue regeneration is urgently designed for augmented under pathological milieu.Methods Results: Herein, photoactivated soft-hard combined scaffold system (PGCZ) was engineered introducing polydopamine-modified zeolitic imidazolate framework-8-loaded double-network hydrogel (soft matrix component) into 3D-printed poly(ε-caprolactone) (PCL) (hard component).The versatile PGCZ based on PCL thus prepared features highly extracellular matrix-mimicking microstructure, suitable biodegradability mechanical properties, excellent photothermal performance, allowing long-term structural stability support regeneration.Under periodic near-infrared (NIR) irradiation, localized effect triggers on-demand release Zn 2+ , which, together with repeated mild hyperthermia, collectively accelerates proliferation osteogenic differentiation preosteoblasts potently inhibits growth biofilm formation.Additionally, also presents outstanding immunomodulatory ROS scavenging capacities, which regulate M2 polarization macrophages drive functional cytokine secretion, leading pro-regenerative in situ enhanced vascularization.In vivo experiments further demonstrated that conjunction activity remarkably attenuated local inflammatory cascade, initiated endogenous stem cell recruitment neovascularization, orchestrated osteoblast/osteoclast balance, ultimately accelerating regeneration. Ivyspring

Язык: Английский

---

Copper‐Based Composites Nanoparticles Improve Triple‐Negative Breast Cancer Treatment with Induction of Apoptosis‐Cuproptosis and Immune Activation

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(28)

Опубликована: Июль 12, 2024

The synergistic effect of apoptosis and cuproptosis, along with the activation immune system, presents a promising approach to enhance efficacy against triple-negative breast cancer (TNBC). Here, two prodrugs are synthesized: reactive oxygen species (ROS)-responsive prodrug PEG-TK-DOX glutathione (GSH)-responsive PEG-DTPA-SS-CPT. These self-assembled chelated Cu2+ prepare nanoparticle PCD@Cu that simultaneously loaded doxorubicin (DOX), camptothecin (CPT), Cu2+. elevated levels ROS GSH in TNBC cells disrupted structure, leading release Cu+, DOX, CPT depletion GSH. DOX triggered immunogenic cell death (ICD) cells. Simultaneously, downregulated expression copper transporting ATPase 2 (ATP7B), causing significant accumulation ions This further induced aggregation lipoylated dihydrolipoamide S-acetyltransferase (DLAT) downregulation iron-sulfur (Fe-S) cluster proteins, ultimately cuproptosis ICD TNBC. In vitro vivo experiments confirmed activated demonstrating strong anti-tumor capabilities. Moreover, exhibited an excellent biosafety profile. Overall, this study provides strategy for effective therapy.

Язык: Английский

---

Type‐Transformational BioHJzyme Enabled by Composition Modulation‐Mediated Energy Band Engineering for Diabetic Infectious Wound Healing

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract The dilemma of diabetic infectious wound healing lies in inhibiting the pathogenic colonization and regulating hyperglycemia. pivotal anti‐pathogenic efficiency is focused on confined gradually weaken reactive oxygen species (ROS) yield peculiar micromilieu owing to materials transformation/dissolution. There, type‐transformational bio‐heterojunction enzyme (BioHJzyme) with operando composition‐modulation proposed, which consisted by glucose oxidase (GOx) decorated type‐I FeSe 2 /Cu O heterojunction. It exhibits robust catalytic produce ROS. Followed, heterojunction can be transformed into dual Z‐scheme a composition /CuSe/Cu primed acid meliorative energy band. conducive NIR‐induced capabilities improve ROS yield. GOx consume H as an amplifier. combined followed enhanced powerfully remove colonization. On top that, sample downgrade Forkhead box (FoxO) signaling pathway regulate cell cycle, facilitate proliferation, further promote repairment. This work provides effective feasible antibacterial strategy way thinking for healing.

Язык: Английский

---

Preclinical advance in nanoliposome-mediated photothermal therapy in liver cancer

Lipids in Health and Disease, Год журнала: 2025, Номер 24(1)

Опубликована: Янв. 31, 2025

Язык: Английский

---

Low‐Dose Cu Ions Assisted by Mild Thermal Stimulus Inducing Bacterial Cuproptosis‐Like Death for Antibiosis and Biointegration

Advanced Functional Materials, Год журнала: 2023, Номер 34(1)

Опубликована: Сен. 15, 2023

Abstract Methicillin‐resistant Staphylococcus aureus (MRSA) is threatening human health due to its resistance multiple antibiotics. Excessive copper (Cu) ions target the lipoylated proteins of tricarboxylic acid cycle cancer cells, inducing proteotoxic stress and their cuproptosis death. Whether plays a part in killing MRSA by low‐dose supplement Cu remains be explored. Herein, Cu‐doped hydroxyapatite nanorods (PC) are prepared on polyetheretherketone (PEEK) resist infection improve PEEK performance tissue integration with assistance near‐infrared (NIR) irradiation, mechanism against elucidated. Mild photothermal stimulation increases bacterial membrane permeability, accelerating ions’ intake consequently cuproptosis‐like death MRSA. It confirmed aggregation dihydrolipoamide S‐acetyltrans‐ferase (DLAT), deactivation glutathione peroxides 4 (GPX4), destabilization Fe─S cluster ferredoxin (FDX1) lipoyl synthase (LIAS). Fortunately, fibroblast behaviors upregulated NIR‐irradiated PC. In vivo, PC NIR irradiation exhibits outstanding elimination, reduced inflammation response, improved biointegration. Overall, it demonstrated that can induced at non‐cytotoxic dose when cooperated mild heat stimulus, this strategy has greatly promising application improving clinic.

Язык: Английский

---