Targeted delivery strategies: The interactions and applications of nanoparticles in liver diseases

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116702 - 116702

Опубликована: Май 11, 2024

In recent years, nanoparticles have been broadly utilized in various drugs delivery formulations. Nanodelivery systems shown promise solving problems associated with the distribution of hydrophobic and promoted accumulation nanomedicines circulation or organs. However, injection dose (NPs) is much greater than that needed by diseased tissues other words, most NPs are localized off-target do not reach desired tissue With rapid development biodegradable biosafety nanomaterials, nanovectors represent assurance safety. effects also induce concerns about application NPs, especially gene editing tools. Therefore, a complete understanding biological responses to body will clearly guide design targeted NPs. The different properties nanodelivery may diverse interactions between carriers this review, we describe relationship liver, influenced organ systemic administration nanoplatforms. Various transport vehicles adopted multiple strategies for cells homeostasis liver liver. Additionally, provide novel strategy treating incurable diseases. appearance has profoundly improved

Язык: Английский

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Liver cirrhosis: molecular mechanisms and therapeutic interventions

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 17, 2024

Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to tissues hepatocytes, along with increased vascular tone portal hypertension. Among them, fibrosis necessary stage essential feature cirrhosis, effective antifibrosis strategies are commonly considered key treating cirrhosis. Although different therapeutic aimed at reversing or preventing have been developed, effects not be more satisfactory. In this review, we discussed abnormal changes in microenvironment that contribute progression highlighted importance recent strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, gut remediation, regulate Meanwhile, for nanoparticles discussed, as their possible underlying broad application prospects ameliorating Finally, also reviewed major challenges opportunities nanomedicine‒biological environment interactions. We hope review will provide insights into pathogenesis mechanisms thus facilitating new methods, drug discovery, better treatment

Язык: Английский

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Silybin: A Review of Its Targeted and Novel Agents for Treating Liver Diseases Based on Pathogenesis

Phytotherapy Research, Год журнала: 2024, Номер unknown

Опубликована: Сен. 23, 2024

Liver disease represents a significant global public health concern. Silybin, derived from Silybum marianum, has been demonstrated to exhibit range of beneficial properties, including anti-inflammatory, antioxidative, antifibrotic, antiviral, and cytoprotective effects. These attributes render it promising candidate for the treatment liver fibrosis, cirrhosis, cancer, viral hepatitis, non-alcoholic fatty disease, other conditions. Nevertheless, its low solubility bioavailability have emerged as limitations in clinical application. To address these limitations, researchers developed number silybin formulations. This study presents comprehensive review results research on diseases recent decades, with particular focus novel formulations based pathogenesis disease. include approaches targeting via CD44 receptor, folic acid, vitamin A, others. Furthermore, findings studies that employed nanotechnology enhance silybin. includes use nanoparticles, liposomes, nanosuspensions. reviews application preparations diseases. However, further high-quality more complete experimental are still required gain understanding efficacy safety preparations. Finally, considers issues arise during

Язык: Английский

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Modulating Fibrotic Mechanical Microenvironment for Idiopathic Pulmonary Fibrosis Therapy

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

Idiopathic pulmonary fibrosis (IPF) is exacerbated by injurious mechanical forces that destabilize the microenvironment homeostasis, leading to alveolar dysfunction and exacerbating disease severity. However, given inherent mechanosensitivity of fibrotic lungs, where type II epithelial cells (AEC IIs) are subjected persistent stretching overactivated myofibroblasts experience malignant interactions during mechanotransduction, it becomes imperative develop effective strategies modulate microenvironment. Herein, cyclo (RGDfC) peptide-decorated zeolitic imidazolate framework-8 nanoparticles (named ZDFPR NPs) constructed target repair aberrant force levels in pathological lungs. Specifically, reduces tension AEC IIs pH-responsive NPs release zinc ions 7, 8-dihydroxyflavone promote differentiation. Meanwhile, between myofibroblast contractility extracellular matrix stiffness mechanotransduction disrupted fasudil inhibition ROCK signaling pathway. The results show successfully restored homeostasis terminated process bleomycin-induced mice. This study not only presents a promising strategy for modulating but also pioneers novel avenue IPF treatment.

Язык: Английский

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Advances in intrahepatic and extrahepatic vascular dysregulations in cirrhotic portal hypertension

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Янв. 31, 2025

Cirrhotic portal hypertension, the most prevalent and clinically significant complication of liver cirrhosis, manifests as elevated venous pressure is associated with severe complications. Although much research on mechanisms hypertension has focused fibrosis, less attention been given to role intrahepatic extrahepatic vascular dysfunction, particularly respect vasculature. While hepatic fibrosis in cirrhotic undeniable, underlying involving vasculature are highly complex. Sinusoidal capillarization endothelial dysfunction contribute increased resistance. Hemodynamic changes circulation, including splanchnic vasodilation hyperdynamic play a development hypertension. Additionally, therapeutic strategies targeting these diverse, improvement sinusoidal microcirculation, therapies stellate cells activation, pharmacological modulation systemic tone. Therefore, this review, we will discuss vascular-related treatment progress cirrhosis provide new theoretical basis practical guidance for clinical treatment.

Язык: Английский

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Engineered MSCs Break Endothelial‐Myofibroblast Crosstalk in Pulmonary Fibrosis: Reconstructing the Vascular Niche

Advanced Materials, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Abstract In the progress of pulmonary fibrosis (PF), normal vascular niche plays a crucial role in alveolar regeneration by secreting angiocrine factors. However, malignant interaction between myofibroblasts and endothelial cells results significant loss capillaries fibroblast foci, which promotes continuous deterioration fibrosis. Herein, an engineered mesenchymal stem cell (MSC) therapeutic named MSC‐MM@LPHN is developed for reconstructing niche, formed modifying surface MSC with ROS‐responsive lipid polymeric hybrid nanoparticles encapsulating metformin macitentan. Due to homing ability MSC, can effectively target lung tissue, then induce myofibroblast dedifferentiation reduce secretion cytokines that cause damage preventing from turning into fibrotic phenotype, leading recovery function. Combined MSC‐secreted growth factors promoting angiogenesis, ultimately constructs structure area reverses bleomycin‐induced PF. The findings suggest targeting network treat PF, provides novel strategy fibrosis‐related diseases.

Язык: Английский

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Combined Esculentin-2CHa Fusion Protein-Coated Au Nanoparticles for Effective Against Non-Alcoholic Fatty Liver Disease in Mice Model

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 3407 - 3421

Опубликована: Март 1, 2025

Extensive research has focused on identifying effective treatments for NAFLD, with numerous bioactive peptide candidates showing significant promise. In this research, a long-acting esculentin-2CHa(1-30)-coated AuNPs (ESC-ABD-AuNPs) was developed and the applicability evaluated their use in treatment of non-alcoholic fatty liver disease (NAFLD). ESC-ABD-AuNPs were synthesized by adopting 1-step reduction process successful preparation nanoparticles (NPs) assessed various physical characterizations including transmission electron microscopy (TEM), ultraviolet-visible (UV-VIS) absorption spectra, dynamic light scattering (DLS), Fourier Transform Infrared Spectroscopy (FT-IR). After prepared, cytotoxicity, pharmacokinetics (PK), biodistribution profiles identified. Then, high-fat diet (HFD)-fed obese mice model, efficacy studies carried out effects anti-hyperglycemia anti-NAFLD. Furthermore, feasibility loading small molecule onto NPs potential combination therapy. an average hydrodynamic size 120 (±10) nm demonstrated good stability extended plasma half-life 28.3 h. The exhibited high accumulation well tolerated cell viability tests. PK studies, showed prolonged retention major organs, such as pancreas liver. Therapeutic HFD-fed mice, where significantly reduced blood glucose levels, improved tolerance, mitigated fat accumulation. platform also therapies, its ability to load obeticholic acid (OCA), farnesoid X receptor (FXR) agonist, found NAFLD clinical studies. Overall, study promising novel NAFLD. This suggests that could be advancement drug delivery treatment, particularly therapies.

Язык: Английский

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Ultrasound‐Mediated Biomimetic Microbubbles Effectively Reverse LSECs Capillarization and Exert Antiplatelet Therapy in Liver Fibrosis

Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Abstract Liver fibrosis, characterized by excessive tissue remodeling as a response to chronic liver injury, is accompanied capillarization of sinusoidal endothelial cells (LSECs) and activated hepatic stellate (HSCs). Simvastatin (Sim) can modulate function increasing nitric oxide synthase (eNOS)‐dependent (NO) release, thereby reversing attenuating fibrosis. However, monotherapy often demonstrates limited therapeutic effectiveness given the complex pathophysiology Herein, type multifunctional liposomal microbubbles (MBs) carrying both Sim platelet membrane (PM) has been designed for drug delivery targeting inflammatory LSECs, with ultrasound‐targeted microbubble destruction (UTMD) mediate efficient release these agents inside sinusoidal. In rat fibrosis model, MBs reverses through increase eNOS‐dependent NO production. Subsequently, adhering LSECs block adhesion activation inherent (PLT), decreasing platelet‐derived growth factor β (PDGF‐β) inhibit HSCs activation. This study strong efficacy integrating PLT against which highlights great potential effectively managing this intractable disease.

Язык: Английский

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Sulfur dioxide-releasing nanomotors improve the therapeutic effect of liver fibrosis by restoring the fenestrae of sinusoids

Journal of Colloid and Interface Science, Год журнала: 2025, Номер unknown, С. 137557 - 137557

Опубликована: Апрель 1, 2025

Язык: Английский

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Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies

Biomolecules, Год журнала: 2024, Номер 14(12), С. 1485 - 1485

Опубликована: Ноя. 22, 2024

Hedgehog (Hh) signaling is a well-established developmental pathway; it crucial for early embryogenesis, cell differentiation, and damage-driven regeneration. It being increasingly recognized that dysregulated Hh also involved in fibrotic diseases, which are characterized by excessive extracellular matrix deposition compromises tissue architecture function. As in-depth insights into the mechanisms of obtained, its complex involvement fibrosis gradually illuminated. Notably, some Hh-targeted inhibitors currently under exploration preclinical clinical trials as means to prevent progression. In this review, we provide concise overview biological signaling. We summarize latest advances our understanding roles fibrogenesis across liver, kidneys, airways, lungs, well other tissues organs, with an emphasis on both shared features and, more critically, distinct functional variations observed these organs. thus highlight context dependence signaling, discuss current status challenges therapies fibrosis.

Язык: Английский

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