Neutrophil‐Mimetic, ROS Responsive, and Oxygen Generating Nanovesicles for Targeted Interventions of Refractory Rheumatoid Arthritis DOI
Zhuang Tang, Shiyu Meng, Xiaoxue Yang

et al.

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

Published: Dec. 12, 2023

Abstract Rheumatoid arthritis (RA) is the most prevalent inflammatory joint disease worldwide, leading to irreversible disability and even mortality. Unfortunately, current treatment regimens fail cure RA due low therapeutic responses off‐target side effects. Herein, a neutrophil membrane‐cloaked, natural anti‐arthritic agent leonurine (Leo), catalase (CAT) co‐loaded nanoliposomal system (Leo@CAT@NM‐Lipo) constructed remodel hostile microenvironment for remission. Due inflammation tropism inherited from neutrophils, Leo@CAT@NM‐Lipo can target accumulate in inflamed cavity where high‐level ROS be catalyzed into oxygen by CAT simultaneously accelerate drug release alleviate hypoxia at lesion site. Besides, membrane camouflaging also enhances anti‐inflammatory potentials of robustly absorbing pro‐arthritogenic cytokines chemokines. Consequently, successfully alleviated paw swelling, reduced score, mitigated bone cartilage damage, reversed multiple organ dysfunctions adjuvant‐induced rats (AIA) synergistic effects macrophage polarization, resolution, scavenging, relief. Furthermore, manifested excellent biocompatibility both cellular animal levels. Taken together, study provided neutrophil‐mimetic responsive nanoplatform targeted therapy represented promising paradigm variety inflammation‐dominated diseases.

Language: Английский

Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis DOI Creative Commons

Ni Yang,

Miaomiao Li,

Ling Wu

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 13, 2023

Macrophage polarization determines the production of cytokines that fuel initiation and evolution rheumatoid arthritis (RA). Thus, modulation macrophage might represent a potential therapeutic strategy for RA. However, coordinated macrophages in synovium synovial fluid has not been achieved thus far. Herein, we develop biomimetic ApoA-I mimetic peptide-modified neutrophil membrane-wrapped F127 polymer (R4F-NM@F127) targeted drug delivery during RA treatment. Due to high expression adhesion molecules chemokine receptors on neutrophils, membrane coating can endow nanocarrier with synovitis-targeting ability, subsequent recruitment under chemotactic effects IL-8. Moreover, R4F peptide modification further endows ability target SR-B1 receptor, which is highly expressed fluid. Long-term vivo imaging shows R4F-NM@F127 preferentially accumulates inflamed joints engulfed by macrophages. After loading anti-inflammatory celastrol (Cel), R4F-NM@F127-Cel significant reduction hepatotoxicity, effectively inhibits inflammation alleviates joint damage reprogramming polarization. our results highlight as promising option treatment

Language: Английский

Citations

33
Advances in Enantiomer-Dependent Nanotherapeutics DOI
Yuwen Wang, Andy Tay

ACS Nano, Journal Year: 2023, Volume and Issue: 17(11), P. 9850 - 9869

Published: June 2, 2023

The nanoscale properties of nanomaterials, especially nanoparticles, including size, shape, and surface charge, have been extensively studied for their impact on nanomedicine. Given the inherent chiral nature biological systems high enantiomeric selectivity, there is rising interest to manipulate chirality nanomaterials enhance biomolecular interactions improve nanotherapeutics. Chiral nanostructures are currently more prevalently used in biosensing diagnostic applications owing distinctive physical optical properties, but they hold great promise use In this Review, we first discuss stereospecific between biomolecules before comparing synthesis characterization methods nanoparticles nanoassemblies. Finally, examine nanotherapeutics cancer, immunomodulation, neurodegenerative diseases propose plausible mechanisms which interact with cells manipulation. This Review a timely reminder arsenal modifications boost research

Language: Английский

Citations

28
Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia DOI Creative Commons
Shamsuddin A. Bhuiyan, Mengyi Xu,

Lite Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 5, 2023

Abstract Peripheral sensory neurons in the dorsal root ganglion (DRG) and trigeminal (TG) are specialized to detect transduce diverse environmental stimuli including touch, temperature, pain central nervous system. Recent advances single-cell RNA-sequencing (scRNA-seq) have provided new insights into diversity of ganglia cell types rodents, non-human primates, humans, but it remains difficult compare transcriptomically defined across studies species. Here, we built cross-species harmonized atlases DRG TG that describe 18 neuronal 11 non-neuronal 6 species 19 studies. We then demonstrate utility this reference atlas by using annotate newly profiled nuclei/cells from both human highly regenerative axolotl. observe transcriptomic profiles neuron subtypes broadly similar vertebrates, expression functionally important neuropeptides channels can vary notably. The resources data presented here guide future comparative transcriptomics, simplify type nomenclature differences studies, help prioritize targets for therapy development.

Language: Английский

Citations

26
Oral Administration of Multistage Albumin Nanomedicine Depots (MANDs) for Targeted Efficient Alleviation of Chronic Inflammatory Diseases DOI

Fangke Zhang,

Yawei Du, Jiancheng Zheng

et al.

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(9)

Published: Jan. 13, 2023

Abstract Methotrexate (MTX) by oral taking has been employed as the first‐line medication for various chronic inflammatory diseases treatment, such Crohn's disease and rheumatoid arthritis (RA). However, administration of MTX very limited clinical benefits will be discontinued due to suboptimal response severe adverse effects on intestinal mucosa. Herein, a multistage albumin nanomedicine depot (denoted MAND) is formulated encapsulating MTX‐loaded human serum nanoparticles (MTX@HSA NPs) into calcium alginate chitosan microcapsules using gas‐shearing technology. The MANDs can provide protection MTX@HSA NPs with well‐persisted biologic activity against gastric acid erosion realize specific boost release in tract mild basic circumstance. absorbed intestine selectively accumulate inflammation lesion exploiting targeting ability HSA. In animal experiments, show improved therapeutic efficacy treatment both RA colitis minimized side respect free administration. Therefore, this conceived promote more clinic popularity enhanced diseases.

Language: Английский

Citations

24
Redox regulation of macrophages DOI Creative Commons
Nhien Tran, Evanna L. Mills

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103123 - 103123

Published: March 12, 2024

Redox signaling, a mode of signal transduction that involves the transfer electrons from nucleophilic to electrophilic molecule, has emerged as an essential regulator inflammatory macrophages. reactions are driven by reactive oxygen/nitrogen species (ROS and RNS) redox-sensitive metabolites such fumarate itaconate which can post-translationally modify specific cysteine residues in target proteins. In past decade our understanding how ROS, RNS, control macrophage function expanded dramatically. this review, we discuss latest evidence regulate is dysregulated with disease. We highlight key tools assess redox signaling important questions remain.

Language: Английский

Citations

15
Musculoskeletal Organs‐on‐Chips: An Emerging Platform for Studying the Nanotechnology–Biology Interface DOI Creative Commons
Yuwen Wang, Patrick Shu‐Hang Yung, Gang Lü

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: March 16, 2024

Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their translation requires a deep understanding complex interplay between nanotechnology MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative versatile microphysiological platform to replicate dynamics tissue microenvironment studying nanotechnology-biology interactions. This review first covers recent advances applications OoCs ability mimic biophysical biochemical stimuli encountered by tissues. Next, integrating into OoCs, cellular responses behaviors may be investigated precisely controlling manipulating nanoscale environment. Analysis disease mechanisms, particularly bone, joint, muscle degeneration, drug screening development personalized medicine greatly facilitated using OoCs. Finally, future challenges directions outlined field, including advanced sensing technologies, integration immune-active components, enhancement biomimetic functionality. By highlighting emerging this aims advance intricate nanotechnology-MSK biology interface its significance in management, therapeutic interventional strategies.

Language: Английский

Citations

12
Nanomedicines targeting activated immune cells and effector cells for rheumatoid arthritis treatment DOI

Yasi Deng,

Hao Zheng, Bin Li

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 371, P. 498 - 515

Published: June 12, 2024

Language: Английский

Citations

11
A Less‐is‐More Strategy for Mitochondria‐Targeted Photodynamic Therapy of Rheumatoid Arthritis DOI

Qingting Zuo,

Jiayan Lyu,

Xinran Shen

et al.

Small, Journal Year: 2024, Volume and Issue: 20(25)

Published: Jan. 15, 2024

Abstract Conventional photodynamic therapy (PDT) of rheumatoid arthritis (RA) faces a dilemma: low‐power is insufficient to kill pro‐inflammatory cells while high‐power exacerbates inflammation. Herein, mitochondrial targeting introduced in PDT RA implement “less‐is‐more” strategy, where higher apoptosis are achieved with lower laser power. In arthritic rats, chlorine 6‐loaded and mitochondria‐targeting liposomes (Ce6@M‐Lip) passively accumulated inflamed joints, entered macrophages, actively localized mitochondria, leading enhanced dysfunction under irradiation. By effectively disrupting macrophages more susceptible PDT, resulting increased initiation. Additionally, it identifies that irradiation caused cell rupture release endogenous danger signals recruited activated additional macrophages. contrast, irradiation, Ce6@M‐Lip not only prevented inflammation but also reduced macrophage infiltration cytokine secretion. Overall, mitochondria reconciled therapeutic efficacy inflammation, thus enabling efficacious yet inflammation‐sparing for RA. This highlights the promise resolve dilemma between anti‐inflammatory inflammatory exacerbation by implementing strategy.

Language: Английский

Citations

10
Bio-nanoparticles loaded with synovial-derived exosomes ameliorate osteoarthritis progression by modifying the oxidative microenvironment DOI Creative Commons

Haifei Cao,

Wan-Xin Li, Hao Zhang

et al.

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

Published: May 20, 2024

Abstract Background and aims Osteoarthritis (OA) is a prevalent degenerative joint disorder, marked by the progressive degeneration of cartilage, synovial inflammation, subchondral bone hyperplasia. The tissue plays pivotal role in cartilage regulation. Exosomes (EXOs), small membrane-bound vesicles released cells into extracellular space, are crucial mediating intercellular communication facilitating exchange information between tissues. Our study aimed to devise hydrogel microsphere infused with SOD3-enriched exosomes (S-EXOs) protect introduce novel, effective approach for OA treatment. Materials methods We analyzed single-cell sequencing data from 4247 obtained GEO database. Techniques such as PCR, Western Blot, immunofluorescence (IF), assays measure oxidative stress levels were employed validate cartilage-protective properties identified key protein, SOD3. In vivo, mice received intra-articular injections S-EXOs bearing microspheres, effectiveness was assessed using safranine O (S.O) staining IF. Results Single-cell analysis suggested that synovium influences via exocrine release findings revealed purified enhanced antioxidant capacity chondrocytes, maintained matrix metabolism stability. S-EXO group showed significant reduction mitoROS ROS 164.2% ( P < 0.0001) 142.7% 0.0001), respectively, compared IL-1β group. Furthermore, exhibited increased COL II ACAN levels, increments 2.1-fold 3.1-fold over Additionally, decrease MMP13 ADAMTS5 protein expression 42.3% 44.4% respectively. It found S-EXO-containing microspheres could effectively deliver SOD3 significantly mitigate progression. OARSI score markedly decreased Conclusion demonstrated secreted fibroblasts exert protective effect on laden offer promising therapeutic alternative

Language: Английский

Citations

10
NLRP3 overexpression exacerbated synovium tissue degeneration in juvenile collagen-induced arthritis DOI Creative Commons
Fater A. Khadour, Younes A. Khadour, Tao Xu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 27, 2025

Juvenile idiopathic arthritis (JIA) can lead to synovial inflammation. JIA is a chronic autoimmune inflammatory condition that primarily affects children. It recognized as the most prevalent form of in pediatric population and associated with significant impairment disability. As an regulator, Nod-like receptor 3 (NLRP3) has been implicated various diseases. However, specific mechanism by which NLRP3 impacts progress remains unclear. Therefore, we conducted this study investigate on inflammation juvenile collagen-induced (CIA). The CIA model was established using Sprague‒Dawley (SD) rats aged 2–3 weeks. In study, investigated potential role regulating NLRP3–NF-κB axis rats. To verify effect JIA, expression knocked down or overexpressed adeno-associated virus injected into knee joint observed plays important development CIA, knocking inhibited alleviated synovium We also demonstrated increased tissue, could upregulate NF-κB signal pathway influence Moreover, found increases impairs autophagy capacity activation pyroptosis results interferes CIA. These provide new insight suggest targeting inflammasome may represent promising therapeutic strategy for managing JIA.

Language: Английский

Citations

1