Active microneedle patch equipped with spontaneous bubble generation for enhanced rheumatoid arthritis treatment

Theranostics, Journal Year: 2025, Volume and Issue: 15(8), P. 3424 - 3438

Published: Feb. 24, 2025

Rationale: The utilization of dissolving microneedles (MNs) facilitates the painless delivery pharmaceuticals via transdermal route. However, conventional MNs rely on passive diffusion through gradual matrix, which can impede therapeutic efficacy delivered drugs. Methods: In this study, we present development a novel degradable active platform. This platform employs sodium bicarbonate and citric acid loaded in patch as built-in motor for deeper faster intradermal payload delivery. microparticles undergo chemical reaction when contact with tissue fluid, resulting rapid formation explosive carbon dioxide bubbles. provides necessary force to break dermal barriers enhance Results: results demonstrated that possessed excellent mechanical properties, detachment characteristics, superior drug release kinetics. Furthermore, permeation behavior exhibited enhanced distribution skin-mimicking gel porcine skin compared MNs. vivo experiments employing rat model rheumatoid arthritis showed achieved Conclusions: universal effective autonomous dynamic microneedle technology is straightforward prepare ultilize, has potential improve drugs, offering significant prospects diverse range applications.

Language: Английский

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Potential mechanisms of rheumatoid arthritis therapy: Focus on macrophage polarization

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113058 - 113058

Published: Sept. 4, 2024

Language: Английский

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Advancements in p53-Based Anti-Tumor Gene Therapy Research

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5315 - 5315

Published: Nov. 11, 2024

The p53 gene is one of the genes most closely associated with human tumors and has become a popular target for tumor drug design. Currently, p53-based therapy techniques have been developed, but these therapies face challenges such as immaturity, high safety hazards, limited efficacy, low patient acceptance. However, researchers are no less enthusiastic about treatment because its theoretical potential to treat cancer. In this paper, advances in related nucleic acid delivery technologies were reviewed prospected order support further development field.

Language: Английский

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Human Serum Albumin‐Coated ¹⁰B Enriched Carbon Dots as Targeted “Pilot Light” for Boron Neutron Capture Therapy

Advanced Science, Journal Year: 2024, Volume and Issue: 11(43)

Published: Sept. 26, 2024

Abstract Boron neutron capture therapy (BNCT) is a physiologically focused radiation that relies on nuclear and fission processes. BNCT regarded as one of the most promising treatments due to its excellent accuracy, short duration therapy, low side effects. The creation novel boron medicines with high selectivity, ease delivery, boron‐effective load current research topic. Herein, boron‐containing carbon dots (BCDs) their human serum albumin (HSA) complexes (BCDs‐HSA) are designed synthesized drugs for BNCT. BCDs ( 10 B: 7.1 wt%) BCDs‐HSA exhibited excitation‐independent orange fluorescent emission which supported use fluorescence imaging tracking B in vivo. introduction HSA enabled exhibit good biocompatibility increased tumor accumulation. active passive targeting abilities explored detail. Subcutaneous RM‐1 tumors B16‐F10 both significantly decrease BNCT, consists injecting then irradiating area neutrons. In short, this study provides strategy delivery may broaden perspectives design nanomedicine

Language: Английский

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In situ polymeric nanomicelle-generating dissolving microneedle patch for enhanced transdermal methotrexate delivery in rheumatoid arthritis treatment

European Polymer Journal, Journal Year: 2024, Volume and Issue: 210, P. 113008 - 113008

Published: April 1, 2024

Language: Английский

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Synergistic rheumatoid arthritis therapy by interrupting the detrimental feedback loop to orchestrate hypoxia M1 macrophage polarization using an enzyme-catalyzed nanoplatform

Bioactive Materials, Journal Year: 2024, Volume and Issue: 41, P. 221 - 238

Published: July 23, 2024

Language: Английский

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ML385, an Nrf2 Inhibitor, Synergically Enhanced Celastrol Triggered Endoplasmic Reticulum Stress in Lung Cancer Cells

ACS Omega, Journal Year: 2024, Volume and Issue: 9(43), P. 43697 - 43705

Published: Oct. 15, 2024

Lung cancer is one of the leading causes death. Celastrol a natural product that has shown anticancer activity but not yet been applied in clinical settings due to its narrow therapeutic window. In this study, we discovered celastrol stimulates an abnormal rise reactive oxygen species (ROS) level lung cells and ROS scavenger N-acetylcysteine (NAC) could counteract cell death caused by celastrol. At same time, upregulated expression cytoprotective transcription factor Nrf2 downstream proteins, which are effective preventing oxidative damage accumulation. Notably, found overexpression enhances tolerance H460 with Keap1 mutation insensitive This indicates increase contributes survival cells. Thus, brought inhibitor ML385 suppress activation Nrf2. We when were added together rates decreased more detected became much higher compared treatment alone. also suppressed HO-1 GCLC, amplified celastrol-induced ATF4/CHOP-dependent endoplasmic reticulum stress (ER stress). Above all, our study enhanced increases ER stress, research provides potential strategy for preclinical investigation

Language: Английский

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Immunomodulatory Supramolecular Hydrogel for Rheumatoid Arthritis Management via Adenosine A2A Receptor-Mediated Macrophage Remodeling

Published: Jan. 1, 2025

Language: Английский

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NaHS@Cy5@MS@SP nanoparticles improve rheumatoid arthritis by inactivating the Hedgehog signaling pathway through sustained and targeted release of H2S into the synovium

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

Published: March 8, 2025

Aberrant proliferation and inflammation of fibroblast-like synoviocytes (FLSs) significantly contribute to the pathogenesis rheumatoid arthritis (RA). Deficiency hydrogen sulfide (H2S) is a driving force for development RA, short half-life H2S-releasing donor sodium hydrosulfide (NaHS) limits its clinical application in RA therapy. Designing targeted delivery system with slow-release properties FLSs could offer novel strategies treating RA. Herein, we designed strategy achieve slow release H2S synovium, which was accomplished by synthesizing NaHS-CY5@mesoporous silic@LNP peptide Dil (NaHS@Cy5@MS@SP) nanoparticles. Our results demonstrated that NaHS@Cy5@MS@SP effectively targets FLSs, upregulates its-producing enzyme cystathionine-γ-lyase (CSE) joints arthritic mice. Overexpression CSE inhibited proliferation, migration, upon lipopolysaccharide (LPS) exposure, effects were mimicked NaHS@Cy5@MS@SP. In vivo studies showed achieved threefold higher AUCinf than free NaHS, improving bioavailability NaHS. Further, synovial hyperplasia reduced bone cartilage erosion DBA/1J mouse model collagen-induced (CIA), superior RNA sequencing molecular validated inactivated Hedgehog signaling pathway as evidenced reductions protein expression SHH, SMO, GLI1 phosphorylated p38/MAPK. This study highlights promising controlled synoviocytes, offering potential management.

Language: Английский

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Endoplasmic Reticulum-Dependent Apoptotic Response to Cellular Stress in Patients with Rheumatoid Arthritis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2489 - 2489

Published: March 11, 2025

Rheumatoid arthritis (RA) is a chronic, common autoimmune disease. It characterized by inflammatory polyarthritis, which can lead to permanent disability in patients. Current treatment mainly symptom-related, aiming reduce pain and inflammation, but does not full recovery. This includes non-steroidal anti-inflammatory drugs (NSAIDs) disease-modifying anti-rheumatic (DMARDs). has been shown that, due chronic reduced glucose levels hypoxia, endoplasmic reticulum (ER) stress induced RA patients, leading the activation of multiple signaling pathways, including ER-dependent adaptation unfolded protein response (UPR) pathway. The aim this study was assess level apoptosis patients diagnosed with RA. sought investigate whether UPR correlated induction could serve as potential diagnostic marker or therapeutic target. In vitro studies have that pathway activity be observed group consisted PBMC cells from 61 individuals, total 31 rheumatoid 30 healthy controls. order validate activation, we estimated molecular markers ER via RT-qPCR expression analysis. GAPDH used standard control. Elevated mRNA for eIF2α (p-value = 0.001903), BBC3 (PUMA) 0.007457 × 10−7) TP53 0.002212) were confirmed Further analysis showed after percentage DNA contained tail 37.78% higher than control 0.0003) measured comet assay. exogenous damage caused hydrogen peroxide found statistically elevated caspase-3 calculated 40.17% controls 0.0028). also more sensitive apoptotic induction. Our results flow cytometry. most important finding our data confirmation sensitivity patients; 40.23% early 0.0105). may help feasibility application diagnosis targeted therapy selected UPR-dependent inhibitors.

Language: Английский

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