mRNA nanodelivery systems: targeting strategies and administration routes DOI Creative Commons
Mujie Yuan, Zeyu Han, Yan Liang

et al.

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

With the great success of coronavirus disease (COVID-19) messenger ribonucleic acid (mRNA) vaccines, mRNA therapeutics have gained significant momentum for prevention and treatment various refractory diseases. To function efficiently in vivo overcome clinical limitations, demands safe stable vectors a reasonable administration route, bypassing multiple biological barriers achieving organ-specific targeted delivery mRNA. Nanoparticle (NP)-based systems representing leading vector approaches ensure successful intracellular to target organ. In this review, chemical modifications types advanced NPs, including lipid NPs polymers are summarized. The importance passive targeting, especially endogenous active targeting nano-delivery is emphasized, different cellular endocytic mechanisms discussed. Most importantly, based on above content physiological structure characteristics organs vivo, design strategies cells classified Furthermore, influence routes highlighted. Finally, an outlook remaining challenges future development toward therapies precision medicine provided.

Language: Английский

Liver macrophages in health and disease DOI Creative Commons
Martin Guilliams, Charlotte L. Scott

Immunity, Journal Year: 2022, Volume and Issue: 55(9), P. 1515 - 1529

Published: Sept. 1, 2022

Language: Английский

Citations

221
Oxidative Stress in Liver Pathophysiology and Disease DOI Creative Commons
Abdolamir Allameh,

Reyhaneh Niayesh‐Mehr,

Azadeh Aliarab

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(9), P. 1653 - 1653

Published: Aug. 22, 2023

The liver is an organ that particularly exposed to reactive oxygen species (ROS), which not only arise during metabolic functions but also the biotransformation of xenobiotics. disruption redox balance causes oxidative stress, affects function, modulates inflammatory pathways and contributes disease. Thus, stress implicated in acute injury pathogenesis prevalent infectious or chronic diseases such as viral hepatitis B C, alcoholic fatty disease, non-alcoholic disease (NAFLD) steatohepatitis (NASH). Moreover, plays a crucial role progression fibrosis, cirrhosis hepatocellular carcinoma (HCC). Herein, we provide overview on effects pathophysiology mechanisms by promotes

Language: Английский

Citations

147
Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options DOI Open Access
Zuzanna Sas, Ewa Cendrowicz, Isabel Weinhäuser

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3778 - 3778

Published: March 29, 2022

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe the USA recent decades. Among different subtypes cancers, hepatocellular carcinoma (HCC) most commonly diagnosed cancer. Besides advances diagnosis promising results pre-clinical studies, HCC remains a highly lethal disease. In many cases, an effect chronic inflammation, which leads to formation complex tumor microenvironment (TME) composed immune stromal cells. TME patients challenge for therapies, as it involved metastasis development resistance. However, given that intricate system cells interacting cells, new immune-based therapies are being developed target HCC. Therefore, understanding complexity will provide possibilities design novel more effective immunotherapeutics combinatorial overcome resistance treatment. this review, we describe role inflammation during progression by focusing on TME. We also therapeutic possible treatment options.

Language: Английский

Citations

116
Lipid nanoparticles (LNPs) for in vivo RNA delivery and their breakthrough technology for future applications DOI
Michaela Jeong, Yeji Lee, Jeongeun Park

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 200, P. 114990 - 114990

Published: July 7, 2023

Language: Английский

Citations

94
Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications DOI
Jiulong Li, Chunying Chen, Tian Xia

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(11)

Published: Jan. 14, 2022

Nanomaterials (NMs) are widely used in commercial and medical products, such as cosmetics, vaccines, drug carriers. Exposure to NMs via various routes dermal, inhalation, ingestion has been shown gain access the systemic circulation, resulting accumulation of liver. The unique organ structures blood flow features facilitate liver sequestration NMs, which may cause adverse effects Currently, most vivo studies focused on at level evaluation gross changes structure functions, however, cell-type-specific uptake responses, well molecular mechanisms cellular levels leading lagging. Herein, authors systematically review diverse interactions with liver, specifically major cell types including Kupffer cells (KCs), sinusoidal endothelial (LSECs), hepatic stellate (HSCs), hepatocytes detailed involved. In addition, knowledge gained nano-liver that can development safer nanoproducts nanomedicine is also reviewed.

Language: Английский

Citations

92
Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies DOI
Isabella Lurje, Nadine T. Gaisa, Ralf Weiskirchen

et al.

Molecular Aspects of Medicine, Journal Year: 2023, Volume and Issue: 92, P. 101191 - 101191

Published: May 24, 2023

Language: Английский

Citations

67
From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications DOI Creative Commons
Andrea Boccatonda,

Lorenzo Andreetto,

Damiano D’Ardes

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 883 - 883

Published: March 13, 2023

Non-alcoholic fatty liver disease (NAFLD) is defined as a chronic characterized by excessive fat accumulation in the without another obvious cause (no alcohol consumption, hepatotoxic medications, toxins, viral infections, genetic hepatic diseases), therefore it an exclusion diagnosis. The term NAFLD literally refers to non-alcohol related hepatopathy and does not adequately correlate with metabolic dysfunction cardiovascular risks. Therefore, researchers scientific societies have moved towards changing terminology. novel nomenclature for metabolic-associated (MAFLD) has been proposed 2020 group of experts overcome issues old diagnosis MAFLD based on presence steatosis at least one between these three conditions: type 2 diabetes mellitus (T2DM), obesity or dysregulation. shown be independent risk factor diseases atherosclerosis. It better main factors atherosclerosis than NAFLD, such dyslipidemia, T2DM hypertension. aim this review highlight reasons why moving MAFLD, what are conceptual basis choice its clinical implications, particularly field.

Language: Английский

Citations

65
The evolving role of liver sinusoidal endothelial cells in liver health and disease DOI
Matthew J. McConnell, Enis Kostallari, Samar H. Ibrahim

et al.

Hepatology, Journal Year: 2023, Volume and Issue: 78(2), P. 649 - 669

Published: Jan. 3, 2023

LSECs are a unique population of endothelial cells within the liver and recognized as key regulators homeostasis. also play role in disease, dysregulation their quiescent phenotype promotes pathological processes including inflammation, microvascular thrombosis, fibrosis, portal hypertension. Recent technical advances single-cell analysis have characterized distinct subpopulations themselves with high resolution defined gene expression profile phenotype, broadening our understanding mechanistic biology. This article will review 4 broad LSEC biology general: (1) heterogeneity, (2) aging senescence, (3) regeneration, (4) inflammation then various pathologies DILI, alcohol-associated NASH, viral hepatitis, transplant rejection, ischemia reperfusion injury. The conclude discussion gaps knowledge areas for future research.

Language: Английский

Citations

61
In vivo liver function reserve assessments in alcoholic liver disease by scalable photoacoustic imaging DOI Creative Commons
Tong Sun, Jing Lv,

Xingyang Zhao

et al.

Photoacoustics, Journal Year: 2023, Volume and Issue: 34, P. 100569 - 100569

Published: Nov. 7, 2023

We present a rapid and high-resolution photoacoustic imaging method for evaluating the liver function reserve (LFR). To validate its accuracy, we establish alcoholic disease (ALD) models employ dual-wavelength spectral unmixing to assess oxygen metabolism. An empirical mathematical model fits signals, obtaining metabolism curve LFR parameters. Liver significantly drops in ALD with emergence of abnormal hepatic lobular structure. ICG half-life remarkably extends from 241 568 s ALD. A significant decline occurs terminal region compared central region, indicated by 106.9 delay half-life, likely due artery vein damage causing hypoxia inadequate nutrition. Reduced glutathione repairs 43% improvement reducing alcohol-induced oxidative damage. Scalable shows immense potential assessing alcoholic-related diseases, providing assistance early detection management disease.

Language: Английский

Citations

59
Use of a Liver-Targeting Immune-Tolerogenic mRNA Lipid Nanoparticle Platform to Treat Peanut-Induced Anaphylaxis by Single- and Multiple-Epitope Nucleotide Sequence Delivery DOI Creative Commons
Xiao Xu, Xiang Wang, Yu‐Pei Liao

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(5), P. 4942 - 4957

Published: Feb. 28, 2023

While oral desensitization is capable of alleviating peanut allergen anaphylaxis, long-term immune tolerance the sought-after goal. We developed a liver-targeting lipid nanoparticle (LNP) platform to deliver mRNA-encoded epitopes liver sinusoidal endothelial cells (LSECs), which function as robust tolerogenic antigen-presenting that induce FoxP3+ regulatory T-cells (Tregs). The mRNA strand was constructed by including nucleotide sequences encoding for nonallergenic MHC-II binding T-cell epitopes, identified in dominant allergen, Ara h2. These were inserted downstream an targeting sequence, further endowed vitro with 5′ and 3′ capping sequences, PolyA tail, uridine substitution. Codon-optimized used microfluidics synthesis LNPs ionizable cationic lipid, also decorated lipid-anchored mannose ligand LSEC targeting. Biodistribution confirmed vivo imaging, while ELISpot assays demonstrated increase IL-10-producing Tregs spleen. Prophylactic administration tandem-repeat or combination encapsulated h2 induced effects C3H/HeJ mice, sensitized subsequently challenged crude extract. In addition physical manifestations there suppression Th2-mediated cytokine production, IgE synthesis, mast cell release, accompanied increased IL-10 TGF-β production peritoneum. Similar efficacy during LNP postsensitization. nondecorated particles had lesser but significant effects, PolyA/LNP-Man lacked protective effects. results demonstrate exciting application mRNA/LNP treatment food promise be widely applicable allergy field.

Language: Английский

Citations

55