Nanomedicines Reprogram Synovial Macrophages by Scavenging Nitric Oxide and Silencing CA9 in Progressive Osteoarthritis

Advanced Science, Journal Year: 2023, Volume and Issue: 10(11)

Published: Feb. 7, 2023

Osteoarthritis (OA) is a progressive joint disease characterized by inflammation and cartilage destruction, its progression closely related to imbalances in the M1/M2 synovial macrophages. A two-pronged strategy for regulation of intracellular/extracellular nitric oxide (NO) hydrogen protons reprogramming macrophages proposed. The combination carbonic anhydrase IX (CA9) siRNA NO scavenger "two-in-one" nanocarriers (NAHA-CaP/siRNA nanoparticles) developed OA therapy scavenging inhibiting CA9 expression In vitro experiments demonstrate that these NPs can significantly scavenge intracellular similar levels as those normal group downregulate mRNA (≈90%), thereby repolarizing M1 into M2 phenotype increasing pro-chondrogenic TGF-β1 (≈1.3-fold), chondrocyte apoptosis. Furthermore, vivo show have great anti-inflammation, protection repair effects, effectively alleviating both monoiodoacetic acid-induced early late mouse models surgical destabilization medial meniscus-induced rat model. Therefore, siCA9 delivery system potential efficient treatment.

Language: Английский

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Using Cu‐Based Metal–Organic Framework as a Comprehensive and Powerful Antioxidant Nanozyme for Efficient Osteoarthritis Treatment

Advanced Science, Journal Year: 2024, Volume and Issue: 11(13)

Published: Jan. 26, 2024

Abstract Developing nanozymes with effective reactive oxygen species (ROS) scavenging ability is a promising approach for osteoarthritis (OA) treatment. Nonetheless, numerous lie in their relatively low antioxidant activity. In certain circumstances, some of these may even instigate ROS production to cause side effects. To address challenges, copper‐based metal–organic framework (Cu MOF) nanozyme designed and applied OA Cu MOF exhibits comprehensive powerful activities (i.e., SOD‐like, CAT‐like, •OH activities) while negligible pro‐oxidant (POD‐ OXD‐like activities). Collectively, more at various types than other Cu‐based antioxidants, such as commercial CuO single‐atom nanozyme. Density functional theory calculations also confirm the origin its outstanding enzyme‐like activities. vitro vivo results demonstrate that an excellent decrease intracellular levels relieve hypoxic microenvironment synovial macrophages. As result, can modulate polarization macrophages from pro‐inflammatory M1 anti‐inflammatory M2 subtype, inhibit degradation cartilage matrix efficient The biocompatibility protective properties make it valuable asset treating ROS‐related ailments beyond OA.

Language: Английский

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Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 3, 2024

Abstract Lymphatic vessels, comprising the secondary circulatory system in human body, play a multifaceted role maintaining homeostasis among various tissues and organs. They are tasked with serious of responsibilities, including regulation lymph absorption transport, orchestration immune surveillance responses. vessel development undergoes series sophisticated regulatory signaling pathways governing heterogeneous-origin cell populations stepwise to assemble into highly specialized lymphatic networks. Lymphangiogenesis, as defined by new vessels sprouting from preexisting vessels/embryonic veins, is main developmental mechanism underlying formation expansion networks an embryo. However, abnormal lymphangiogenesis could be observed many pathological conditions has close relationship progression diseases. Mechanistic studies have revealed set lymphangiogenic factors cascades that may serve potential targets for regulating lymphangiogenesis, further modulate Actually, increasing number clinical trials demonstrated promising interventions showed feasibility currently available treatments future translation. Targeting promoters or inhibitors not only directly regulates but improves efficacy diverse treatments. In conclusion, we present comprehensive overview physiological functions, describe critical involvement multiple Moreover, summarize targeting therapeutic values providing novel perspectives treatment strategy

Language: Английский

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Nanoparticle-Mediated Multiple Modulation of Bone Microenvironment To Tackle Osteoarthritis

ACS Nano, Journal Year: 2024, Volume and Issue: 18(15), P. 10625 - 10641

Published: April 2, 2024

Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN size 268 nm are stable under physiological conditions, be specifically taken up by macrophages through FN-mediated targeting, dissociated in oxidative microenvironment. dendrimer having intrinsic anti-inflammatory property FN both antioxidative properties display integrated functions ROS scavenging, hypoxia attenuation, macrophage M2 polarization, thus protecting from apoptosis creating designed bone immune microenvironment stem cell osteogenic differentiation. These characteristics lead to their effective treatment an OA model vivo reduce pathological changes joints including synovitis inhibition cartilage matrix degradation simultaneously promote differentiation repair. developed combining advantages bioactive treat may immunomodulatory therapy different diseases.

Language: Английский

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Electrosprayed core–shell microspheres co-deliver fibronectin and resveratrol for combined treatment of acute lung injury

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 686, P. 498 - 508

Published: Jan. 31, 2025

Language: 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, Journal Year: 2025, Volume and Issue: 380, P. 469 - 489

Published: Feb. 11, 2025

Language: Английский

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Amelioration of Osteoarthritis via Tetrahedral Framework Nucleic Acids Delivering Microrna‐124 for Cartilage Regeneration

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(46)

Published: July 9, 2023

Abstract MicroRNAs (miRNAs) regulate several physiological and pathological processes involved in various diseases, including osteoarthritis (OA). OA is the most common global musculoskeletal disorder, characterized by irreversible progressive destruction of articular cartilage. Supplementation with exogenous miRNAs may represent a promising therapeutic treatment, miRNA‐124 (miR‐124) being prime candidate for its anti‐inflammatory ability; however, an effective drug delivery system urgently required to enhance miR‐124 stability capacity enter chondrocytes. To this end, tetrahedral framework nucleic acids’ (tFNAs) self‐assembled 3D DNA nanostructures possess superior inherent biocompatibility, versatile functionality, unsurpassed editability, strong cellular internalization ability. In study, tFNAs carrying one or three (T‐miR1 T‐miR3) are successfully synthesized. T‐miR3 largely absorbed via induced inflammatory chondrocytes IL‐1β. With reactive oxygen species’ scavenging ability inflammation‐suppressive release behavior, efficiently protects against IL‐1β injury vitro. Additionally, effectively prevents progression inhibiting chondrocyte apoptosis, smoothing cartilage surfaces, suppressing extracellular matrix degradation, increasing synovial thickness, protecting vivo cartilage, illustrating treatment. This study provides experimental evidence novel strategies treatment clinical setting.

Language: Английский

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Inflammation‐Regulated Auto Aggregated Hydrogel Microspheres Via Anchoring Cartilage Deep Matrix for Genes Delivery

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(51)

Published: Aug. 11, 2023

Abstract The high density structure of cartilage matrix negative charge seriously hinders the penetration and enrichment drugs/genes into tissue. In this study, hexachlorocyclotriphosphonitrile is used as core to prepare self‐polymerized phosphorus dendrimers with inflammatory reaction through substitution condensation reaction. vector can achieve efficient damaged articular (slightly acidic condition) effective anchoring (normal physiological size effect under response. Meanwhile, a gene “delivery library,” G1‐NC5.HCl@siRNA gradually released microspheres degrading; long‐term silencing specific genes realized. Further, loaded hydrogel by ionic bond coordination microfluidic techniques improve residency in joint cavity. results vitro vivo e xperiments show that complex has better at pH = 6.6, decreases 7.6, which effectively anchor site for continuous drug delivery. composite significantly degeneration osteoarthritis (OA) promote regeneration. Therefore, microsphere delivery system response promising penetrant/anchoring carrier OA treatment.

Language: Английский

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Musculoskeletal Organs‐on‐Chips: An Emerging Platform for Studying the Nanotechnology–Biology Interface

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

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Applications of Hydrogels in Osteoarthritis Treatment

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 923 - 923

Published: April 22, 2024

This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite known for superior mechanical properties enhanced biodegradability. spotlights novel such as injectable microneedle technology, responsive which have revolutionized OA treatment through targeted efficient therapeutic delivery. Moreover, it discusses innovative hydrogel including protein-based superlubricating potential to reduce joint friction inflammation. The integration of bioactive compounds within hydrogels augment efficacy also examined. Furthermore, the anticipates continued technological deeper understanding hydrogel-based therapies. It emphasizes provide tailored, minimally invasive treatments, thus highlighting critical role advancing dynamic field biomaterial science management.

Language: Английский

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