Polydopamine Nanoparticles Targeting Ferroptosis Mitigate Intervertebral Disc Degeneration Via Reactive Oxygen Species Depletion, Iron Ions Chelation, and GPX4 Ubiquitination Suppression

Advanced Science, Journal Year: 2023, Volume and Issue: 10(13)

Published: March 23, 2023

Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe

Language: Английский

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Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy

ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 9126 - 9139

Published: April 25, 2023

Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member the B7 superfamily, associated with poor survival glioblastoma (GBM) patients. Moreover, dimer EGCG (dEGCG) synthesized this work enhanced IFN-γ-induced ferroptosis cells vitro vivo. Herein, we prepared recombinant anti-B7-H3×CD3 biAbs constructed MMP-2-sensitive S-biAb/dEGCG@NPs offer combination treatment strategy for efficient systemic GBM elimination. Given targeted delivery microenvironment responsiveness, displayed intracranial accumulation, 4.1-, 9.5-, 12.3-fold higher than that biAb/dEGCG@NPs, biAb/dEGCG complexes, free biAbs, respectively. Furthermore, 50% GBM-bearing mice S-biAb/dEGCG@NP group survived longer 56 days. Overall, can induce elimination boosting effect enhancing immune checkpoint blockade (ICB) immunotherapy may be successful antibody nanocarriers cancer therapy.

Language: Английский

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Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(18)

Published: Jan. 15, 2024

Abstract Mitochondria, widely known as the energy factories of eukaryotic cells, have a myriad vital functions across diverse cellular processes. Dysfunctions within mitochondria serve catalysts for various diseases, prompting widespread demise. Mounting research on remedying damaged indicates that constitute valuable target therapeutic intervention against diseases. But less clinical practice and lower recovery rate imply limitation traditional drugs, which need further breakthrough. Nanotechnology has approached favorable regiospecific biodistribution high efficacy by capitalizing excellent nanomaterials targeting drug delivery. Mitochondria‐remedying nanodrugs achieved ideal effects. This review elucidates significance in cells organs, while also compiling mortality data related Correspondingly, nanodrug‐mediate strategies applicable mitochondria‐remedying disease are detailed, with full understanding roles dysfunction advantages nanodrugs. In addition, future challenges directions discussed. conclusion, this provides comprehensive insights into design development nanodrugs, aiming to help scientists who desire extend their fields engage interdisciplinary subject.

Language: Английский

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Transformable Supramolecular Self‐Assembled Peptides for Cascade Self‐Enhanced Ferroptosis Primed Cancer Immunotherapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(21)

Published: Feb. 10, 2024

Abstract Immunotherapy has received widespread attention for its effective and long‐term tumor‐eliminating ability. However, immunogenic “cold” tumors, such as prostate cancer (PCa), the low immunogenicity of tumor itself is a serious obstacle to efficacy. Here, this work reports strategy enhance PCa by triggering cascade self‐enhanced ferroptosis in cells, turning from “hot”. This develops transformable self‐assembled peptide TEP‐FFG‐CRApY with alkaline phosphatase (ALP) responsiveness glutathione peroxidase 4 (GPX4) protein targeting. self‐assembles into nanoparticles under aqueous conditions transforms nanofibers response ALP during endosome/lysosome uptake promoting lysosomal membrane permeabilization (LMP). On one hand, released TEP‐FFG‐CRAY target GPX4 selectively degrade light irradiation, inducing ferroptosis; on other large amount leaked Fe 2+ further amplify through Fenton reaction. TEP‐FFG‐CRApY‐induced improves cell maturation dendritic cells (DCs) increasing intratumor T‐cell infiltration. More importantly, recovered T secreting amounts interferon‐gamma (IFN‐γ). provides novel molecular design synergistic molecularly targeted therapy tumors.

Language: Английский

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Catalytic Nanodots‐Driven Pyroptosis Suppression in Nucleus Pulposus for Antioxidant Intervention of Intervertebral Disc Degeneration

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(19)

Published: Feb. 1, 2024

Abstract Low back pain resulting from intervertebral disc degeneration (IVDD) is a prevalent global concern; however, its underlying mechanism remains elusive. Single‐cell sequencing analyses revealed the critical involvement of pyroptosis in IVDD. Considering reactive oxygen species (ROS) as primary instigator and lack an efficient intervention approach, this study developed carbonized Mn‐containing nanodots (MCDs) ROS‐scavenging catalytic biomaterials to suppress nucleus pulposus (NP) cells efficiently alleviate Catalytic MCDs have superior efficacy scavenging intracellular ROS rescuing homeostasis NP microenvironment compared with N‐acetylcysteine, classical antioxidant. The data validates that plays vital role mediating protective effects against oxidative stress. Systematic vivo assessments substantiate effectiveness puncture‐induced IVDD rat model, further demonstrating their ability pyroptosis. This highlights potential antioxidant nanomedicine inhibitor mechanistically unveils strategy for treatment

Language: Английский

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Rescuing Nucleus Pulposus Cells from ROS Toxic Microenvironment via Mitochondria‐Targeted Carbon Dot‐Supported Prussian Blue to Alleviate Intervertebral Disc Degeneration

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(8)

Published: Jan. 15, 2024

Abstract Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration mitochondrial function and senescence nucleus pulposus cells (NPCs). Significantly, the main ROS production site non‐immune mitochondria, suggesting mitochondria a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which known as mitochondrial‐tropic ligands, utilized modify carbon dot‐supported Prussian blue (CD‐PB) scavenge superfluous intro‐cellular maintain NPCs at normal redox levels. CD‐PB‐TPP can effectively escape from lysosomal phagocytosis, permitting efficient targeting. After strikingly lessening via exerting antioxidant enzyme‐like activities, such superoxide dismutase, catalase, rescues damaged senescence, catabolism, inflammatory reaction vitro. Imaging evaluation tissue morphology assessment vivo suggest that height index, mean grey values tissue, histological are significantly improved IVDD model after locally performed. In conclusion, this study demonstrates ROS‐induced dysfunction leads possesses enormous potential rescue pathological process through removal targeting supplying neoteric strategy for treatment.

Language: Английский

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Selenoprotein‐Regulated Hydrogel for Ultrasound‐Controlled Microenvironment Remodeling to Promote Bone Defect Repair

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(12)

Published: Jan. 14, 2024

Abstract Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede repair processes. Herein, an innovative ultrasound‐modulatable hydrogel platform with selenoprotein‐mediated antioxidant effects to promote injury is presented. This encapsulates oxygen‐enriched selene‐incorporated thin‐shell silicon methacrylate gelatin (O 2 ‐PSSG). The resultant construct orchestrates modulation bone‐defect microenvironment, thereby expediting course regeneration. Ultrasound (US) used regulate pore size release selenium‐containing nanoparticles in situ synthesis efficient intracellular selenoproteins hydrogen peroxide consumption. As expected, O ‐PSSG rapidly releases selenocystine ([Sec] ) under US control scavenge maintain homeostasis marrow mesenchymal stem cells (BMSCs). Over time, action system by selenoprotein increases activation Wnt/β‐catenin pathways promotes differentiation BMSCs. Consequently, potentiates proficiency BMSCs both vitro vivo, alleviates environments, osteogenic differentiation, expedites cranial rat models. In summary, this study suggests designed constructed US‐responsive a promising prospective strategy for addressing fostering

Language: Английский

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Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration

Small, Journal Year: 2023, Volume and Issue: 20(13)

Published: Nov. 12, 2023

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available effectively delay IVDD. This study develops multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on nanoparticles via Schiff base bond, imparts multifunctionality the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting mitochondria scavenge excess species. The scavenging activity against originates polyphenol-based structures within nanoparticles. Furthermore, Pyroptosis blocked inhibiting Gasdermin mediated pore formation membrane rupture. successfully reduces activation nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome protein (Gasdermin D, GSDMD) oligomerization, leading reduced expression Nod-like receptors. multifaceted approach demonstrates higher efficiency in Pyroptosis. Experimental results confirm that preserves height, retains water content, tissue structure. These findings highlight potential improving IVDD provide novel insights for future research treatments.

Language: Английский

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Evaluation of Reactive Oxygen Species Scavenging of Polydopamine with Different Nanostructures

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 13(4)

Published: Nov. 4, 2023

Abstract Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress‐related diseases, while excessive accumulation of ROS will lead to genetic changes cells promote the occurrence inflammatory diseases or cell death. Nature‐inspired polydopamine (PDA) with tailored nanostructures emerges as scavenger is considered effective approach inflammation‐related diseases. However, effects nanoparticle structure on PDA scavenging efficacy efficiency remain uncovered. In this work, three typical nanoparticles including solid PDA, mesoporous hollow are synthesized, which physiochemical properties characterized. Furthermore, their performance investigated by vitro evaluation radical removal. Among nanoparticles, demonstrated have highest capability, mainly due its specific surface area. Finally, study vivo inflammation models constructed. The results confirm that most potent more reducing reperfusion injury, improving renal function, preventing periodontitis progression, respectively. Together good biosafety biocompatibility profiles, particular, can be a promising avenue fight against

Language: Английский

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Targeting the Labile Iron Pool with Engineered DFO Nanosheets to Inhibit Ferroptosis for Parkinson's Disease Therapy

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(41)

Published: Sept. 2, 2024

Ferroptosis in neurons is considered one of the key factors that induces Parkinson's disease (PD), which caused by excessive iron accumulation intracellular labile pool (LIP). The ions released from LIP lead to aberrant generation reactive oxygen species (ROS) trigger ferroptosis and exacerbate PD progression. Herein, a pioneering design multifunctional nanoregulator deferoxamine (DFO)-integrated nanosheets (BDPR NSs) presented target restrict protect against PD. BDPR NSs are constructed incorporating brain-targeting peptide DFO into polydopamine-modified black phosphorus nanosheets. These can sequester free ions, thereby ameliorating overload regulating metabolism. Furthermore, decrease lipid peroxidation mitigating ROS accumulation. More importantly, specifically accumulate mitochondria suppress mitochondrial In vivo experiments demonstrated highly efficiently mitigated dopaminergic neuronloss its associated behavioral disorders modulating inhibiting ferroptosis. Thus, BDPR-based nanovectors holds promise as potential avenue for advancing therapy.

Language: Английский

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