Opsonization Inveigles Macrophages Engulfing Carrier‐Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy

Advanced Science, Год журнала: 2024, Номер 11(22)

Опубликована: Апрель 9, 2024

Abstract Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated an imbalance of M1/M2 macrophages in the synovial cavities contributes to progression, regulating M1 M2 polarization can be potential therapeutic strategy. Basing on inherent immune mechanism pathological environment OA, immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) developed, its evaluated. After intra‐articular administration, IgG conjugation facilitates recognition engulfment nanoparticles macrophages. The internalized disassemble response increased oxidative stress, released bilirubin (BR) JPH203 scavenge reactive oxygen species (ROS), inhibit nuclear factor kappa‐B pathway, suppress activated mammalian target rapamycin result repolarization enhance M2/M1 ratios. Suppression IgG/BRJ promotes protection repair rat model, thereby improving outcomes. This strategy opsonization involving engulf carrier‐free BR/JPH203 therapy holds great intervention treatment.

Язык: Английский

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Sequential Targeting Chondroitin Sulfate‐Bilirubin Nanomedicine Attenuates Osteoarthritis via Reprogramming Lipid Metabolism in M1 Macrophages

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Abstract The infiltration and excessive polarization of M1 macrophages contribute to the induction persistence low‐grade inflammation in joint‐related degenerative diseases such as osteoarthritis (OA). lipid metabolism dysregulation promotes macrophage by coordinating compensatory pathways inflammatory oxidative stress responses. Here, a self‐assembling, licofelone‐loaded nanoparticle (termed LCF‐CSBN), comprising chondroitin sulfate bilirubin joined an ethylenediamine linker, is developed selectively reprogram activation. LCF‐CSBN internalized via CD44‐mediated endocytosis targets Golgi apparatus accompanied with reactive oxygen species‐responsive release licofelone (LCF, dual inhibitor arachidonic acid metabolism). effectively M2 transition reprogramming apparatus‐related sphingolipid metabolism. Intra‐articularly injected retains joint for up 28 days accumulates into macrophages. Moreover, can attenuate inflammation, stress, cartilage degeneration OA model rats. These findings indicate promising potential lipid‐metabolism‐reprogramming targeted therapy OA.

Язык: Английский

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Metabolic reprogramming of macrophages by a nano-sized opsonization strategy to restore M1/M2 balance for osteoarthritis therapy

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 469 - 489

Опубликована: Фев. 11, 2025

Язык: Английский

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Ultrasmall Prussian Blue Nanozyme Attenuates Osteoarthritis by Scavenging Reactive Oxygen Species and Regulating Macrophage Phenotype

Nano Letters, Год журнала: 2024, Номер 24(37), С. 11697 - 11705

Опубликована: Сен. 3, 2024

Osteoarthritis (OA) is a degenerative joint disease characterized by obscure etiology and unsatisfactory therapeutic outcomes, making the development of new efficient therapies urgent. Superfluous reactive oxygen species (ROS) have historically been considered one crucial factors inducing pathological progression OA. Ultrasmall Prussian blue nanoparticles (USPBNPs), approximately sub-5 nm in size, are developed regulating configuration polyvinylpyrrolidone chains. USPBNPs display an excellent ROS eliminating capacity catalase-like activity, capable decomposing hydrogen peroxide (H

Язык: Английский

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Carrier-Free Nanodrugs: From Bench to Bedside

ACS Nano, Год журнала: 2024, Номер 18(35), С. 23827 - 23841

Опубликована: Авг. 20, 2024

Carrier-free nanodrugs with extraordinary active pharmaceutical ingredient (API) loading (even 100%), avoidable carrier-induced toxicity, and simple synthetic procedures are considered as one of the most promising candidates for disease theranostics. Substantial studies commercial success "carrier-free" nanocrystals have demonstrated their strong clinical potential. However, practical translations remain challenging impeded by unpredictable assembly processes, insufficient delivery efficiency, an unclear in vivo fate. In this Perspective, we systematically outline contemporary emerging carrier-free based on diverse APIs, well highlight opportunities challenges translation. Looking ahead, further improvements design preparation, drug delivery, efficacy, safety nanomedicines essential to facilitate translation from bench bedside.

Язык: Английский

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Application and progress of smart hydrogel microspheres for regulating oxidative stress in osteoarthritis

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160620 - 160620

Опубликована: Фев. 1, 2025

Язык: Английский

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Adaptive bilirubin nanoscavenger alleviates pulmonary oxidative stress and inflammation for acute lung injury therapy

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Acute lung injury (ALI) is a life-threatening condition characterized by rapidly progressing respiratory distress and hypoxemia. Oxidative stress-induced inflammation in tissue plays crucial role the progression of ALI. Excessive generation reactive oxygen species (ROS) pulmonary microenvironment activates inflammatory signaling pathways, enhancing transcription pro-inflammatory factors ultimately leading to necrosis. Bilirubin (BR), an exceptional endogenous antioxidant, possesses ability counteract elevated levels through direct reactions or inducing antioxidant systems such as Nrf2/HO-1 signaling. However, its limited solubility poses hindrance further applications. Hence, it imperative develop suitable bilirubin-based system for biological utilization. In this study, we developed ROS-sensitive adaptive nanoscavenger (GP@BR) co-assembling bilirubin-conjugated glycol chitosan (GC-BR) polyethylene (PEG-BR), aiming alleviate oxidative stress ALI treatment. The different conjugations endowed bilirubin derivatives with varying sensitivity towards reacting ROS, enabling GP@BR exert antioxidative properties specifically environments on demand. Besides excellent properties, also demonstrated absorb excess cytokines. Moreover, our optimized facilitated transport across mucosal layer epithelial cells. vivo studies confirmed that significantly improved symptoms suppressed fibrosis. This study highlighted potential multiple actions treatment

Язык: Английский

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Osteoimmunology in Osteoarthritis: Unraveling the Interplay of Immunity, Inflammation, and Joint Degeneration

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 4121 - 4142

Опубликована: Март 1, 2025

Osteoarthritis (OA) is a degenerative joint disease influenced by multiple factors, with its etiology arising from intricate interactions among mechanical stress, inflammatory processes, and disruptions in bone metabolism. Recent research immunology indicates that immune-mediated mechanisms significantly contribute to the progression of OA, highlighting immune cells, cytokine networks, components. Immune cells interact osteoclasts, osteoblasts, chondrocytes variety ways. These foster pro-inflammatory microenvironment, contributing cartilage breakdown, synovial inflammation, sclerosis subchondral bone. In this article, we present comprehensive review focusing on critical role their cytokine-mediated feedback loops pathophysiology OA. addition, are exploring novel therapeutic strategies targeting pathways, including macrophage polarization, T-cell differentiation, stem cell therapy restore metabolic balance between immunity By integrating cutting-edge immunology, integrates latest advancements construct framework for unraveling pathogenesis laying theoretical foundation development innovative precision therapies.

Язык: Английский

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Enhancing oocyte in vitro maturation and quality by melatonin/bilirubin cationic nanoparticles: A promising strategy for assisted reproduction techniques

International Journal of Pharmaceutics X, Год журнала: 2024, Номер 8, С. 100268 - 100268

Опубликована: Июль 2, 2024

In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable IVM stands as a strategy. Numerous antioxidants have been explored for IVM, yielding considerable effects; however, several aspects, including solubility, stability, safety, demand attention resolution. this study, we developed nanoparticles by self-assembling endogenous bilirubin melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) alleviate oxidative enhance maturation. The optimized MB@GBn exhibited uniform spherical shape, measuring 128 nm particle size, PDI value 0.1807 surface potential +11.35 mV. positively charged facilitated nanoparticle adherence the through electrostatic interaction, allowing functional action. studies demonstrated that MB@GB significantly enhanced compromised oocytes. Further investigation revealed MB@GB's effectiveness scavenging ROS, reducing intracellular calcium levels, suppressing mitochondrial polarization. This study not only offers novel perspective on nano drug delivery systems biomedical applications but also presents an innovative strategy enhancing IVM.

Язык: Английский

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Nanomedicine revolutionizes epilepsy treatment: overcoming therapeutic hurdles with nanoscale solutions

Expert Opinion on Drug Delivery, Год журнала: 2024, Номер 21(5), С. 735 - 750

Опубликована: Май 3, 2024

Introduction Epilepsy, a prevalent neurodegenerative disorder, profoundly impacts the physical and mental well-being of millions globally. Historically, antiseizure drugs (ASDs) have been primary treatment modality. However, despite introduction novel ASDs in recent decades, significant proportion patients still experiences uncontrolled seizures.

Язык: Английский

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