A Smart MMP‐9‐responsive Hydrogel Releasing M2 Macrophage‐derived Exosomes for Diabetic Wound Healing

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

Chronic diabetic wounds are characterized by prolonged inflammation and excessive accumulation of M1 macrophages, which impede the healing process. Therefore, resolving promptly transitioning to proliferative phase critical steps for effective wound healing. Exosomes have emerged as a promising therapeutic strategy. In this study, smart hydrogel capable responding pathological cues in inflammatory microenvironment promote transition from proliferation delivering M2 macrophage-derived exosomes (M2-Exos) is developed. The synthesized through cross-linking oxidized dextran, matrix metalloproteinase (MMP)-9-sensitive peptide, carboxymethyl chitosan containing M2-Exos. response elevated MMP-9 concentrations microenvironment, demonstrates diagnostic logic, adjusting release kinetics M2-Exos accordingly. on-demand facilitated macrophage polarization phenotype, thereby promoting accelerating transcriptomic analysis further reveals that MMP-9-responsive with delivery exerts anti-inflammatory regenerative effects downregulating inflammation-related pathways. This study introduces an innovative, microenvironment-responsive exosome system enables precise control agent release, offering personalized approach treatment chronic wounds.

Language: Английский

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Extracellular vesicle-mediated bidirectional communication between the liver and other organs: mechanistic exploration and prospects for clinical applications

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

Published: March 8, 2025

The liver, functioning as an endocrine organ, secretes a variety of substances that influence the activities other body organs. Conversely, molecules generated by organs such bone, gut, and adipose tissue can also impact liver function. Accumulating evidence suggests bidirectional communication between However, research on how extracellular vesicles (EVs), which transport active molecular mediators, contribute to this interorgan is still in its nascent stages. EVs are capable transporting functional molecules, including lipids, nucleic acids, proteins, thereby affecting recipient cells across different at biological level. This review examines role facilitating cardiovascular system, pancreas, brain, lungs, kidneys, tissue. It explores their potential disease treatment highlights challenges understanding EV-mediated interactions. contribution mediator-carrying two-way remains area ongoing investigation. Future will provide more comprehensive theoretical foundation clarify precise mechanisms governing organs, pinpoint medical targets, expand application within realm precision medicine.

Language: Английский

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“Sample-In, Result-Out” liquid biopsy chip based on immunomagnetic separation and CRISPR detection for multiplex analysis of exosomal microRNAs

Biosensors and Bioelectronics, Journal Year: 2025, Volume and Issue: unknown, P. 117460 - 117460

Published: April 1, 2025

Language: Английский

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Trojan Horse-Like Vehicles for CRISPR-Cas Delivery: Engineering Extracellular Vesicles and Virus-Like Particles for Precision Gene Editing in Cystic Fibrosis

Human Gene Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

The advent of genome editing has kindled the hope to cure previously uncurable, life-threatening genetic diseases. However, whether this promise can be ultimately fulfilled depends on how efficiently gene agents delivered therapeutically relevant cells. Over time, viruses have evolved into sophisticated, versatile, and biocompatible nanomachines that engineered shuttle payloads specific cell types. Despite advances in safety selectivity, long-term expression sustained by viral vectors remains a cause for concern. Cell-derived vesicles (CDVs) are gaining traction as elegant alternatives. CDVs encompass extracellular (EVs), diverse set intrinsically low-immunogenic membranous nanoparticles, virus-like particles (VLPs), bioparticles with scaffold envelope structures, but devoid material. Both EVs VLPs deliver ribonucleoprotein cargo target cytoplasm, ensuring machinery is only transiently active thereby increasing its safety. In review, we explore natural diversity their potential delivery clustered regularly interspaced short palindromic repeats (CRISPR) machinery. We illustrate different strategies optimization CDV loading retargeting, highlighting versatility tunability these vehicles. Nonetheless, lack robust standardized protocols production, purification, quality assessment still hinders widespread adoption further CRISPR-based therapies advanced "living drugs." believe collective, multifaceted effort urgently needed address critical issues unlock full genome-editing technologies yield safe, easy-to-manufacture, pharmacologically well-defined therapies. Finally, discuss current clinical landscape lung-directed cystic fibrosis could drive significant breakthroughs vivo disease.

Language: Английский

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Inhalable myofibroblast targeting nanoparticles for synergistic treatment of pulmonary fibrosis

Science Advances, Journal Year: 2025, Volume and Issue: 11(18)

Published: May 1, 2025

Pulmonary fibrosis (PF) is a life-threatening interstitial lung disease, characterized by excessive fibroblast activation and collagen deposition, leading to progressive pulmonary function decline limited therapeutic efficacy. Here, the inhalable, myofibroblast-targeted, pH-responsive liposomes (FL-NI) were developed for effective codelivery of nintedanib, mainstream antifibrotic drug in clinic, siIL11, small interfering RNA that silences key profibrosis cytokine IL-11. Notably, FL-NI achieved 117.8% increase delivery noninvasive inhalation 71.5% specifically protein-positive myofibroblasts while reducing nonspecific immune cell epithelial uptake 29.8 55.8%, respectively. The accurate nintedanib siIL11 into synergistic effects, effectively enhanced myofibroblast deactivation, reduced pathological deposition 50.8%, promoted tissue repair. remodeled aberrant microenvironment without inducing systemic toxicities. Therefore, this work demonstrated notable potential pluripotent strategy improving PF outcomes its promising clinical translation.

Language: Английский

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Editorial: Subcellular organelle-targeting of nanomaterials for enhancing therapeutic effectiveness

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 115460 - 115460

Published: Oct. 1, 2024

Language: Английский

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A Single‐Atom Mn/MoO_3−x Nanoagonist for Cascade cGAS/STING Activation in Tumor‐Specific Catalytic Metalloimmunotherapy

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract The cyclic GMP‐AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway plays a crucial role in initiating anti‐tumor immunity. Despite the development various STING agonists, their effectiveness is often limited by suboptimal activation efficiency and poor sustainability. To address this, Mn/MoO 3− x nanoagonist featuring Mn single‐atom sites presented, designed for cascade cGAS/STING tumor‐specific catalytic metalloimmunotherapy. (SANA) meticulously crafted doping atoms into defective molybdenum oxide (MoO ), enabling robust peroxidase‐mimicking catalysis inducing severe double‐stranded DNA (dsDNA) damage tumors. Of note, 2+ MoO 4 2− can be responsively released from SANA enhance sensitivity cGAS to dsDNA. Importantly, with relatively slow‐release profile facile cellular accumulation compensates that has due continuous efflux, thus continuatively triggering secretion type I beyond 72 h. Remarkably, significantly inhibits tumor growth metastasis without supplementary agonists or external stimulation. This study offers promising approach efficacy sustainability

Language: Английский

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