Utilization of Nitrogen-Doped Graphene Quantum Dots to Neutralize ROS and Modulate Intracellular Antioxidant Pathways to Improve Dry Eye Disease Therapy

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2691 - 2708

Published: March 1, 2024

Purpose: Patients afflicted with dry eye disease (DED) experience significant discomfort. The underlying cause of DED is the excessive accumulation ROS on ocular surface. Here, we investigated nitrogen doped-graphene quantum dots (NGQDs), known for their ROS-scavenging capabilities, as a treatment DED. Methods: NGQDs were prepared by using citric acid and urea precursors through hydrothermal method. antioxidant abilities evaluated through: scavenging both extracellular intracellular, regulating nuclear factor-erythroid 2-related factor (Nrf2) pathway human corneal epithelial cells (HCECs) transcription inflammation related genes. Furthermore, modified Arg-Gly-Asp-Ser (RGDS) peptides to obtain RGDS@NGQDs. In vivo , RGDS@NGQDs suspended in 0.1% Pluronic F127 (w/v) delivered drops scopolamine hydrobromide-induced mouse model. Preclinical efficacy was compared healthy DPBS treated mice. Results: These demonstrated pronounced properties, efficiently neutralizing free radicals activating intracellular Nrf2 pathway. vitro studies revealed that H 2 O -exposed HCECs induced preservation cell viability. Additionally, there reduction inflammation-associated To prolong residence time NGQDs, they further RGDS create drops. exhibited superior activity even at low concentrations (10 μg/mL). Subsequent notably mitigated symptoms model, primarily reducing levels. Conclusion: Our findings underscore enhanced benefits achieved modifying GQDs doping peptide tethering. Importantly, our novel formulation effectively ameliorated symptoms, thereby representing therapeutic management. Keywords: disease, antioxidant, doped graphene dots,

Language: Английский

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Design of Highly Adhesive Urchin‐Like Gold Nanostructures for Effective Topical Drug Administration and Symptomatic Relief of Corneal Dryness

Small Structures, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Topical instillation of cyclosporin A (an anti‐inflammatory drug) is clinically recommended as the first‐line treatment for dry eye disease. Nevertheless, it suffers from poor ocular drug retention and cannot comprehensively address corneal dryness‐related symptoms such oxidative stress, angiogenesis, neurodegeneration. Inspired by nanotechnology‐mediated material/biological interactions, in this study, a highly adhesive metallic nanoplatform with an urchin‐like structure designed topical quercetin administration therapy. The gold nanostructures most pronounced branch lengths exhibit strongest cytoadhesion bioadhesion capabilities, which significantly enhance nano‐urchins 150‐fold at 7 days post‐instillation compared smooth‐surfaced nanoparticles. In rabbit model dryness, single‐dose nanoformulation (high quercetin‐functionalized (NU‐Q(H))) demonstrated remarkable efficacy stimulating tear production (30‐fold improvement), inhibiting inflammatory IL‐6 expression (49‐fold attenuating pathological angiogenesis (32‐fold promoting nerve regeneration (18‐fold improvement) to high nanoparticles (NP‐Q(H)). particular, integrity surface, film, meibomian gland restored levels similar those healthy rabbits. These findings suggest promising potential nanobiomaterial structural engineering developing nanomedicines long‐acting eye‐drop formulations disease applications.

Language: Английский

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Suppression of NLRP3/Caspase-1/GSDMD Mediated Corneal Epithelium Pyroptosis Using Melatonin-Loaded Liposomes to Inhibit Benzalkonium Chloride-Induced Dry Eye Disease

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 2447 - 2463

Published: May 1, 2023

Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting dry disease (DED)-like changes ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified have been developed, characterized, used for inhibiting BAC-induced DED (BAC-DED). Methods: The TAT was chemically grafted onto Mal-PEG 2000 -DSPE Michael's addition between sulfhydryl group maleimide -DSPE. TAT-MT-LIPs were prepared using film dispersion followed extrusion method topically treated rats once day. BAC-DED induced topical administration with 0.2% BAC twice daily. Defects, edema, inflammation corneas, well IOP, examined. Histologic analyses corneas performed assess change oxidation NLRP3/Caspase-1/GSDMD signaling transduction. Results: After administration, significantly alleviated DED-clinical symptoms experimental animals tissue preventing loss epithelium conjunctival goblet cells. Our data suggested continuous exposure mediated pyroptosis, not reported before. caused substantial mt-DNA oxidation, promoted transduction consequent pyroptosis. could efficiently suppress pyroptosis subsequent signal transmission. Conclusion: involved development BAC-DED. present study provided new insights adverse effects BAC, can serve target protecting when applying drops. developed inhibit give great potential be treatment. Keywords: melatonin liposome, disease, benzalkonium chloride, axis

Language: Английский

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Carbohydrate polymer-based bioadhesive formulations and their potentials for the treatment of ocular diseases: A review

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 242, P. 124902 - 124902

Published: May 19, 2023

Language: Английский

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Nanomaterials in the diagnosis and treatment of ophthalmic diseases

Nano Today, Journal Year: 2024, Volume and Issue: 54, P. 102117 - 102117

Published: Jan. 4, 2024

Language: Английский

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Bioactive Metal–Organic Frameworks as a Distinctive Platform to Diagnosis and Treat Vascular Diseases

Small, Journal Year: 2024, Volume and Issue: 20(27)

Published: Feb. 5, 2024

Vascular diseases (VDs) pose the leading threat worldwide due to high morbidity and mortality. The detection of VDs is commonly dependent on individual signs, which limits accuracy timeliness therapies, especially for asymptomatic patients in clinical management. Therefore, more effective early diagnosis lesion-targeted treatments remain a pressing need. Metal-organic frameworks (MOFs) are porous crystalline materials formed by coordination inorganic metal ions organic ligands. Due their unique specific surface area, structural flexibility, functional versatility, MOFs recognized as highly promising candidates diagnostic therapeutic applications field VDs. In this review, potential act biosensors, contrast agents, artificial nanozymes, multifunctional agents treatment from perspective, highlighting integration between methods with generalized. At same time, multidisciplinary cooperation chemistry, physics, biology, medicine promote substantial commercial transformation tackling called for.

Language: Английский

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Comprehensive dry eye therapy: overcoming ocular surface barrier and combating inflammation, oxidation, and mitochondrial damage

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

Published: May 9, 2024

Abstract Background Dry Eye Disease (DED) is a prevalent multifactorial ocular disease characterized by vicious cycle of inflammation, oxidative stress, and mitochondrial dysfunction on the surface, all which lead to DED deterioration impair patients’ quality life social functioning. Currently, anti-inflammatory drugs have shown promising efficacy in treating DED; however, such are associated with side effects. The bioavailability less than 5% owing factors as rapid tear turnover presence corneal barrier. This calls for investigations overcome these challenges drug administration. Results A novel hierarchical action liposome nanosystem (PHP-DPS@INS) was developed this study. In terms delivery, PHP-DPS@INS nanoparticles (NPs) overcame surface transport barrier adopting strategy “ocular electrostatic adhesion-lysosomal site-directed escape”. therapy, achieved targeting antioxidant effects through SS-31 peptide, exerted an effect loading insulin reduce inflammatory metabolites. Ultimately, synergistic “anti-inflammation-antioxidation-mitochondrial function restoration” breaks DED. demonstrated remarkable cellular uptake, lysosomal escape, vitro. Targeted metabolomics analysis revealed that effectively normalized elevated level proinflammatory metabolite fumarate vitro hypertonic model DED, thereby reducing levels key (IL-1β, IL-6, TNF-α). Additionally, strongly inhibited reactive oxygen species (ROS) production facilitated structural repair. vivo, treatment significantly enhanced adhesion duration permeability mice, improving bioavailability. It also restored secretion, suppressed damage, reduced inflammation mice. Moreover, it favorable safety profiles both vivo. Conclusion summary, study successfully comprehensive management transmission disrupted dry eye pathogenesis. pioneered regulation metabolites conditions, presenting safe, efficient, innovative therapeutic other diseases.

Language: Английский

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Recent Advances in Nanotechnology for the Treatment of Dry Eye Disease

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(8), P. 669 - 669

Published: April 12, 2024

Dry eye disease (DED) incidence is continuously growing, positioning it to become an emergent health issue over the next few years. Several topical treatments are commonly used treat DED; however, reports indicate that only a minor proportion of drug bioavailability achieved by majority drops available on market. In this context, enhancing ability overcome ocular barriers and prolonging its residence time surface represent new challenge in field carrier systems. Therefore, research has focused development multi-functional nanosystems, such as nanoemulsions, liposomes, dendrimers, hydrogels, other nanosized carriers. These systems designed improve efficacy and, at same time, require fewer daily administrations, with potentially reduced side effects. This review summarizes different nanotechnologies developed, their role DED, nanotechnology-based eyedrops currently approved for DED treatment.

Language: Английский

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Regenerative cerium oxide nanozymes alleviate oxidative stress for efficient dry eye disease treatment

Regenerative Biomaterials, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 1, 2022

Abstract Dry eye disease (DED) is the most common in ophthalmic consultation except for refractive errors. Therefore, an exploration of valid and alternative therapeutic interventions essential to feed urgent medical need. It has been demonstrated that oxidative stress causes multiple adverse effects pathogenesis DED, thence alleviating effective strategy DED treatment. Herein, we developed a cerium oxide nanozyme combined with branched poly(ethylene imine)-graft-poly(ethylene glycol) (bPEI-g-PEG). Owing its stable hydrophilic chains on surface reducing cytotoxicity loads amines groups be ions through coordination bonds, modified nanozymes (referred as CNP@bPEI-g-PEG) are water soluble highly biocompatible. Meanwhile, due excellent antioxidant activity, CNP@bPEI-g-PEG can mimic activity superoxide dismutase catalase scavenge intracellular reactive oxygen species (ROS). Experimental studies firmly were auto-regenerative more active scavenging excessive ROS by cerium-element valence state recycling, recovering morphology corneal, conjunctival epithelium number goblet cells. The advanced combination may offer superior deal treatment DED.

Language: Английский

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Comparative study of cyclosporine A liposomes and emulsions for ophthalmic drug delivery: Process optimization through response surface methodology (RSM) and biocompatibility evaluation

Colloids and Surfaces B Biointerfaces, Journal Year: 2023, Volume and Issue: 225, P. 113267 - 113267

Published: March 14, 2023

Language: Английский

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