Carrier-Free Nanodrug Based on Co-Assembly of Methylprednisolone Dimer and Rutin for Combined Treatment of Spinal Cord Injury

ACS Nano, Journal Year: 2023, Volume and Issue: 17(13), P. 12176 - 12187

Published: June 30, 2023

Spinal cord injury (SCI), which is characterized by excessive inflammatory cell infiltration and accumulation of oxidative substance, would severely impede neurological functional recovery lead to permanent profound neurologic deficits even disability. Methylprednisolone (MP) the most commonly used clinical anti-inflammatory drug for SCI treatment, but high doses are typically required that can cause severe side effects. Here, we developed a carrier-free thioketal linked MP dimer@rutin nanoparticles (MP2-TK@RU NPs) achieve combined treatment coassembling reactive oxygen species (ROS) cleavable dimers rutin. This proposed nanodrug possesses following favorable advantages: (1) system easily accessible has drug-loading capacity, preferred pharmaceutical industry; (2) The ROS-cleavable linker increases efficiency targeted delivery site; (3) Rutin, type plant-derived natural flavonoid with good biocompatibility, anti-inflammatory, antioxidant properties, codelivered enhance therapy outcomes. obtained MP2-TK@RU NPs exhibited potent antioxidative properties both in vitro vivo, demonstrating superior locomotor function neuroprotective efficacy rats SCI. anticipated provide promising therapeutic strategy treatment.

Language: Английский

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Multifunctional Conductive and Electrogenic Hydrogel Repaired Spinal Cord Injury via Immunoregulation and Enhancement of Neuronal Differentiation

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

Published: Feb. 3, 2024

Abstract Spinal cord injury (SCI) is a refractory neurological disorder. Due to the complex pathological processes, especially secondary inflammatory cascade and lack of intrinsic regenerative capacity, it difficult recover function after SCI. Meanwhile, simulating conductive microenvironment spinal reconstructs electrical neural signal transmission interrupted by SCI facilitates repair. Therefore, double‐crosslinked hydrogel (BP@Hydrogel) containing black phosphorus nanoplates (BP) synthesized. When placed in rotating magnetic field (RMF), BP@Hydrogel can generate stable signals exhibit electrogenic characteristic. In vitro, shows satisfactory biocompatibility alleviate activation microglia. RMF, enhances anti‐inflammatory effects. wireless stimulation promotes differentiation stem cells (NSCs) into neurons, which associated with PI3K/AKT pathway. vivo, injectable elicit behavioral electrophysiological recovery complete transected mice alleviating inflammation facilitating endogenous NSCs form functional neurons synapses under RMF. The present research develops multifunctional for repair targeting multiple mechanisms including immunoregulation enhancement neuronal differentiation.

Language: Английский

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Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Spinal cord injury (SCI) is a catastrophic to the central nervous system (CNS) that can lead sensory and motor dysfunction, which seriously affects patients' quality of life imposes major economic burden on society. The pathological process SCI divided into primary secondary injury, cascade amplified responses triggered by injury. Due complexity mechanisms SCI, there no clear effective treatment strategy in clinical practice. Exosomes, are extracellular vesicles endoplasmic origin with diameter 30–150 nm, play critical role intercellular communication have become an ideal vehicle for drug delivery. A growing body evidence suggests exosomes great potential repairing SCI. In this review, we introduce exosome preparation, functions, administration routes. addition, summarize effect mechanism various repair review efficacy combination other strategies Finally, challenges prospects use described.

Language: Английский

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A cryo-shocked M2 macrophages based treatment strategy promoting repair of spinal cord injury via immunomodulation and axonal regeneration effects

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Recovery from spinal cord injury (SCI) is often impeded by neuroinflammation, scar formation, and limited axonal regeneration. To tackle these issues, we developed an innovative biomimetic drug delivery system using liquid nitrogen-treated M2 macrophages (LNT M2) which internalized paclitaxel (PTX) nanoparticles beforehand. These were incorporated into a gelatin methacryloyl (GelMA) scaffold, creating multifunctional, injectable treatment for single-dose administration. The LNT inherited the inflammatory factor/chemokine receptors living thus possessing significant neutralizing effect. In addition, scaffold provides slow, sustained release of PTX, promoting regeneration suppressing formation in SCI rats. M2-based dual-functional significantly enhances motor function, reduces accelerates modulating microenvironment preventing glial fibrotic scars. This approach combines regenerative effects low-dose PTX with immunoregulatory properties M2, leading to remarkable neurological recovery Moreover, scaffold's straightforward preparation, ease standardization, "ready-to-use" nature make it promising candidate acute intervention future clinical applications.

Language: Английский

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Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using recombinant protein CsgA, and its successful application spinal cord injury repair demonstrated. Gelation achieved by physical entanglement CsgA nanofibrils, resulting in self‐supporting at low concentrations (≥5 mg mL −1 ). By leveraging programmability gene sequence, bioactive enhanced fusing functional peptide GHK. GHK recognized anti‐inflammatory, antioxidant, neurotrophic factor‐stimulating properties, making it valuable addition to applications. vitro experiments demonstrate that CsgA‐GHK can modulate microglial M2 polarization, promote neuronal differentiation neural stem cells, inhibit astrocyte differentiation. Additionally, shows efficacy alleviating inflammation promotes regeneration site, leading significant recovery rat model with compression cavity. These findings lay groundwork developing modular design platform hydrogels tissue

Language: Английский

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Engineering of M2 Macrophages‐Derived Exosomes via Click Chemistry for Spinal Cord Injury Repair

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(11)

Published: March 6, 2023

Abstract Spinal cord injury (SCI) is one of the most common causes death and disability. The effective modulation complicated microenvironment, regeneration injured spinal tissue, functional recovery after SCI are still clinical challenges. Recently, macrophages‐derived exosomes have shown great potential for various diseases due to their inflammation‐targeting property. However, further modifications needed endow with neural regenerative recovery. In current study, a novel nanoagent (MEXI) designed treatment by conjugating bioactive IKVAV peptides surface M2 via an easy rapid click chemistry method. vitro, MEXI inhibits inflammation reprograming macrophages promotes neuronal differentiation stem cells. vivo, engineered target site tail vein injection. Furthermore, histological analysis reveals that improves motor mice reducing infiltration macrophages, downregulating pro‐inflammatory factors, improving nervous tissues. Taken together, this study provides strong evidence significance in

Language: Английский

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Emergency Treatment and Photoacoustic Assessment of Spinal Cord Injury Using Reversible Dual‐Signal Transform‐Based Selenium Antioxidant

Small, Journal Year: 2023, Volume and Issue: 19(35)

Published: May 1, 2023

Spinal cord injury (SCI), following explosive oxidative stress, causes an abrupt and irreversible pathological deterioration of the central nervous system. Thus, preventing secondary injuries caused by reactive oxygen species (ROS), as well monitoring assessing recovery from SCI are critical for emergency treatment SCI. Herein, strategy is developed based on selenium (Se) matrix antioxidant system to effectively inhibit stress-induced damage simultaneously real-time evaluate severity using a reversible dual-photoacoustic signal (680 750 nm). Within photoacoustic assessment (ETPSA) strategy, designed Se loaded boron dipyrromethene dye with double hydroxyl group (Se@BDP-DOH) used sensitive reporter excellent eliminating stress. Se@BDP-DOH found promote both spinal tissue locomotor function in mice Furthermore, ETPSA synergistically enhanced ROS consumption via caveolin 1 (Cav 1)-related pathways, confirmed upon Cav siRNA. Therefore, potential tool improving

Language: Английский

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Schwann Cell-Derived Exosomes and Methylprednisolone Composite Patch for Spinal Cord Injury Repair

ACS Nano, Journal Year: 2023, Volume and Issue: 17(22), P. 22928 - 22943

Published: Nov. 10, 2023

Spinal cord injury (SCI) can cause permanent loss of sensory and motor function, there is no effective clinical treatment, to date. Due the complex pathological process involved after injury, synergistic treatments are very urgently needed in practice. We designed a nanofiber scaffold hyaluronic acid hydrogel patch release both exosomes methylprednisolone injured spinal non-invasive manner. This composite showed good biocompatibility stabilization exosome morphology toxicity nerve cells. Meanwhile, increased proportion M2-type macrophages reduced neuronal apoptosis an vitro study. In vivo, functional electrophysiological performance rats with SCI was significantly improved when covered surface hematoma. The inhibited inflammatory response through macrophage polarization from M1 type M2 survival neurons by inhibition SCI. therapeutic effects this be attributed TLR4/NF-κB, MAPK, Akt/mTOR pathways. Thus, provides medicine-exosomes dual-release system may provide method for treatment individuals

Language: Английский

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Cell Development Enhanced Bionic Silk Hydrogel on Remodeling Immune Pathogenesis of Spinal Cord Injury via M2 Polarization of Microglial

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(14)

Published: Jan. 15, 2023

Abstract Due to the complex spatial‐temporal pathophysiology of spinal cord injury (SCI), effective modulation SCI‐specific inflammatory pathogenesis achieve desirable therapeutic effects on functional recovery still remains challenging. Herein, cell‐enhanced photocrosslinked silk fibroin hydrogels with extracellular matrix‐mimicking cues mechanical properties and RGD (Arg‐Gly‐Asp) signals are gelled in situ fill lesion site modulate injury‐induced neuroinflammation promote neurite regrowth after SCI. The bionic hydrogel system provides biomimetic neuronal differentiation neural stem/progenitor cells (NPCs) growth by activating YAP nuclear expression. Importantly, favored strong capacity macrophage/microglia recruitment, NPCs encapsulated ([email protected]) effectively promotes recruited macrophages/microglia M2 polarization releasing S100A4 thereby remodels microenvironment Moreover, [email protected] successfully reduces glial scar formation accelerates corticospinal tract axon improve locomotor recovery. Overall, this work contributes illustrating mechanism development based biomaterial therapies modulating enhanced a promising strategy for

Language: Английский

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Regulatory T cells promote functional recovery after spinal cord injury by alleviating microglia inflammation via STAT3 inhibition

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(8), P. 2129 - 2144

Published: March 13, 2023

Abstract Background Immediately after spinal trauma, immune cells, and proinflammatory cytokines infiltrate the cord disrupt focal microenvironment, which impedes axon regeneration functional recovery. Previous studies have reported that regulatory T cells (Tregs) enter central nervous system exert immunosuppressive effects on microglia during multiple sclerosis stroke. However, whether how Tregs interact with modulate injured microenvironments injury (SCI) remains unknown. Method Regulatory spatiotemporal characteristics were analyzed in a mouse contusion SCI model. Microglia activation status was evaluated by immunostaining RNA sequencing. Cytokine production examined using Luminex. The role of STAT3 Treg–microglia crosstalk investigated transwell isolated primary microglia. Results infiltration peaked day 7 SCI. Treg depletion promoted switch to phenotype. Inflammation‐related genes, such as ApoD , well downstream IL‐6 TNF‐α upregulated Treg‐depleted mice. inhibition involved crosstalk, chemical blockade improved function recovery Conclusion Our results suggest promote alleviating inflammatory reaction via STAT3.

Language: Английский

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