Robust and Multifunctional Nanoparticles Assembled from Natural Polyphenols and Metformin for Efficient Spinal Cord Regeneration

ACS Nano, Journal Year: 2023, Volume and Issue: 17(18), P. 18562 - 18575

Published: Sept. 14, 2023

The treatment of spinal cord injury (SCI) remains unsatisfactory owing to the complex pathophysiological microenvironments at site and limited regenerative potential central nervous system. Metformin has been proven in clinical animal experiments repair damaged structures functions by promoting endogenous neurogenesis. However, early stage acute SCI, adverse microenvironment sites, such as reactive oxygen species inflammatory factor storm, can prevent activation neural stem cells (NSCs) differentiation NSCs into neurons, decreasing whole effect. To address those issues, a series robust multifunctional natural polyphenol-metformin nanoparticles (polyphenol-Met NPs) were fabricated with pH-responsiveness excellent antioxidative capacities. resulting NPs possessed several favorable advantages: First, composed active ingredients different biological properties, without need for carriers; second, feature could allow targeted drug delivery injured site; more importantly, enabled drugs performances exhibit strong synergistic effects. results demonstrated that improved polyphenols boosted activated neurons oligodendrocytes, which efficiently nerve enhance functional recovery SCI rats. This work highlighted design fabrication via efficient microenvironmental regulation activation.

Language: Английский

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Carrier-free self-assembled nanomedicine based on celastrol and galactose for targeting therapy of hepatocellular carcinoma via inducing ferroptosis

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 267, P. 116183 - 116183

Published: Feb. 5, 2024

Language: Английский

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CD44-targeting hyaluronic acid-selenium nanoparticles boost functional recovery following spinal cord injury

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

Published: Jan. 23, 2024

Abstract Background Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant anti-inflammatory properties hampers clinical translation these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed prepared for ROS responses injured cord, enhancing recovery. Results The HA-Se easily through direct reduction seleninic acid presence HA. obtained exhibited a remarkable capacity to eliminate free radicals CD44 receptor-facilitated internalization by astrocytes. Moreover, effectively mitigated secretion proinflammatory cytokines (such as IL-1β, TNF-α, IL-6) microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that could accumulate within lesion site targeting. As result, demonstrated superior protection axons neurons site, leading enhanced rat model SCI. Conclusions These results highlight potential SCI treatment.

Language: Английский

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Dual-sided centripetal microgrooved poly (D,L-lactide-co-caprolactone) disk encased in immune-regulating hydrogels for enhanced bone regeneration

Materials Today Bio, Journal Year: 2025, Volume and Issue: 30, P. 101436 - 101436

Published: Jan. 5, 2025

Well-designed artificial scaffolds are urgently needed due to the limited self-repair capacity of bone, which hampers effective regeneration in critical defects. Optimal must provide physical guidance recruit cells and immune regulation improve regenerative microenvironment. This study presents a novel scaffold composed dual-sided centripetal microgrooved poly(D,L-lactide-co-caprolactone) (PLCL) film combined with dynamic hydrogel containing prednisolone (PLS)-loaded Prussian blue nanoparticles (PB@PLS). The microgrooves on surface PLCL were imprinted using micropatterned polydimethylsiloxane (PDMS) template. Following aminolysis, was covalently grafted EM-7 peptide via glutaraldehyde. Functional group analysis, morphology hydrophilicity evaluated X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), an optical contact angle measuring instrument, respectively. Bone regeneration-related (e.g., bone marrow mesenchymal stem cells, macrophages, Schwann endothelial cells) cultured films tended align along stripes migrate from periphery toward center region vitro. Subsequently, encapsulated immune-regulating synthesized thiol-modified gelatin Cu2+ presence PB@PLS nanoparticles, demonstrated excellent antioxidant properties. significantly accelerated critical-sized regeneration, as evidenced by increase volume newly formed histological images vivo. innovative approach holds substantial promise for clinical applications broader tissue repair.

Language: Английский

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Magnetic Nanoparticles and Methylprednisolone Based Physico‐Chemical Bifunctional Neural Stem Cells Delivery System for Spinal Cord Injury Repair

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: March 22, 2024

Abstract Neural stem cells (NSCs) transplantation is an attractive and promising treatment strategy for spinal cord injury (SCI). Various pathological processes including the severe inflammatory cascade difficulty in stable proliferation differentiation of NSCs limit its application translation. Here, a novel physico‐chemical bifunctional neural delivery system containing magnetic nanoparticles (MNPs methylprednisolone (MP) designed to repair SCI, former regulates through mechanical stimulation chronic phase, while latter alleviates response acute phase. The releases MP promote microglial M2 polarization, inhibit M1 reduce neuronal apoptosis. Meanwhile, tend differentiate into functional neurons with generated by MNPs static field, which related activation PI3K/AKT/mTOR pathway. SCI mice achieve better recovery after receiving via system, has milder inflammation, higher number microglia, more neurons, axonal regeneration. Together, this combined physical chemical drug therapy demonstrated be effective, provides new insights clinical transformation repair.

Language: Английский

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Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles

ACS Nano, Journal Year: 2024, Volume and Issue: 18(19), P. 12117 - 12133

Published: April 22, 2024

Ulcerative colitis is a chronic condition in which dysregulated immune response contributes to the acute intestinal inflammation of colon. Current clinical therapies often exhibit limited efficacy and undesirable side effects. Here, programmable nanomicelles were designed for treatment loaded with RU.521, an inhibitor cyclic GMP-AMP synthase-stimulator interferon genes (cGAS-STING) pathway. STING-inhibiting micelles (SIMs) comprise hyaluronic acid-stearic acid conjugates include reactive oxygen species (ROS)-responsive thioketal linker. SIMs selectively accumulate at site trigger drug release presence ROS. Our vitro studies macrophages vivo murine model demonstrated that leverage HA-CD44 binding target sites inflammation. Oral delivery mice both preventive delayed therapeutic models ameliorated colitis's severity by reducing STING expression, suppressing secretion proinflammatory cytokines, enabling bodyweight recovery, protecting from colon shortening, restoring colonic epithelium. In end points combined metabolomics identified key metabolites role mucosal findings highlight significance platforms downregulate inflammatory pathways mucosa managing bowel diseases.

Language: Английский

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ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair

Bioactive Materials, Journal Year: 2024, Volume and Issue: 38, P. 438 - 454

Published: May 12, 2024

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis one of the main causes neural cell death loss neurological function spinal cord, ferroptosis inhibitors are effective reducing inflammation repairing SCI. Although human umbilical mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments promote regeneration SCI, their efficacy greatly limited by local microenvironment after Therefore, this study, we constructed drug-release nanoparticle system with synergistic Huc-MSCs inhibitor, which anchored Tz-A6 peptide based on CD44-targeting sequence, combined reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at other end for SCI repair. Meanwhile, also modified classic inhibitor Ferrostatin-1 (Fer-1) synthesized new prodrug Feborastatin-1 (Feb-1). The showed treatment regimen significantly inhibited response promoted recovery rats This study developed combination therapy provides strategy construction drug-coordinated system.

Language: Английский

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Self‐Carrier Nanoparticles for Delivery of Paclitaxel and IDO Inhibitor to Boost Antitumor Chemo‐Immunotherapy

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(30)

Published: March 21, 2024

Abstract The combination of chemotherapy and immunotherapy holds great potential in clinical treatment advanced cancers. Whereas, the therapeutic outcome chemotherapeutic immune regulator is suboptimal due to their poor tumor availability severe off‐target toxicity. Herein, self‐carrier nanoparticles (PSMT NPs) integrating a paclitaxel (PTX) prodrug indoleamine 2,3‐dioxygenase 1 (IDO) inhibitor (1‐methyl‐tryptophan, 1MT) for tumor‐specific chemo‐immunotherapy constructed. After internalization by cancer cells, PSMT NPs can respond endogenous redox stimulus, release PTX 1MT. released not only promote cell apoptosis via intervention mitosis but also initiate immunogenic death facilitate recruitment activation tumor‐infiltrating cytotoxic T lymphocytes. concomitant 1MT inhibit IDO activity exhaust regulatory thereby synergistically activating exhibit potentiated antitumor output toward triple‐negative breast negligible systemic This facile versatile nanoplatform provides promising strategy cooperatively activate immunity chemo‐immunotherapy.

Language: Английский

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In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury

ACS Nano, Journal Year: 2024, Volume and Issue: 18(10), P. 7346 - 7362

Published: Feb. 28, 2024

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined SCI. prepared PFCN could release PAH and curcumin response acidic SCI microenvironment. Subsequently, exhibited an effectively neuroprotective effect through scavenging toxic well nitrogen oxygen species neurons, modulating microglial M1/M2 polarization, down-regulating expression inflammation-related cytokines inhibit neuroinflammation. intravenous administration significantly ameliorate malignant injured cord, protect promote motor function recovery contusive rat model.

Language: Английский

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Nanoparticles in Periodontitis Therapy: A Review of the Current Situation

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 6857 - 6893

Published: July 1, 2024

Periodontitis is a disease of inflammation that affects the tissues supporting periodontium. It triggered by an immunological reaction gums to plaque, which leads destruction periodontal attachment structures. one most commonly recognized dental disorders in world and major factor loss adult teeth. Scaling root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like surgery, extractions, planning insufficient halt progression In response problem bacterial resistance, some researchers are committed finding alternative therapies antibiotics. addition, scholars focus new materials provide powerful microenvironment tissue regeneration promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, antioxidant properties, immunomodulatory capacities, promotion bone ability, made them can be used treatment However, there many problems limit clinical translation nanoparticles, such as toxic accumulation cells, poor correlation between vitro vivo, animal-to-human transmissibility. this paper, we review present researches nanoparticles periodontitis from perspective three main categories: inorganic organic nanocomposites (including nanofibers, hydrogels, membranes). The aim comprehensive recent update nanoparticles-based conclusion section summarizes opportunities challenges design

Language: Английский

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