<p>Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate</p>

International Journal of Nanomedicine, Год журнала: 2020, Номер Volume 15, С. 9355 - 9371

Опубликована: Ноя. 1, 2020

Abstract: Exosomes or small extracellular vesicles are considered a new generation of bioinspired-nanoscale drug delivery system (DDS). Endogenous exosomes function as signalosomes since they convey signals via ligands adhesion molecules located on the exosomal membrane, packaged inside exosome. Recently, exosome membrane modification, therapeutic payloads encapsulation, and modulation in vivo disposition have been extensively investigated, among which significant advances made to optimize exosome-mediated solid tumors. Exosomes, specifically tumor cell-derived exosomes, presumed tumor-preferential due homotypic features. However, quality attributes that dictate tissue distribution, cell type-selective uptake, intracellular payload release administered well spatiotemporal information regarding fate vivo, remain be further investigated. This review summarizes recent developing platforms with focus targeting. The pharmacokinetic features naive factors influencing their summarized. Recent strategies improve targeting also reviewed context biological microenvironment (TME). Selected approaches augment deposition methods enhance delivery, summarized emphasis underlying mechanisms (eg, passive active targeting, endosomal escape, etc.). In conclusion, this highlights recently reported tumor-targeting exosome-based it's hope multiple might employed synergistic combination development cancer therapy. Keywords: exosome, tumor-targeting, PK, nanovesicles

Язык: Английский

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Novel therapeutic targets for cholestatic and fatty liver disease

Gut, Год журнала: 2021, Номер 71(1), С. 194 - 209

Опубликована: Окт. 6, 2021

Cholestatic and non-alcoholic fatty liver disease (NAFLD) share several key pathophysiological mechanisms which can be targeted by novel therapeutic concepts that are currently developed for both areas. Nuclear receptors (NRs) ligand-activated transcriptional regulators of metabolic processes including hepatic lipid glucose metabolism, energy expenditure bile acid (BA) homoeostasis, as well inflammation, fibrosis cellular proliferation. Dysregulation these contributes to the pathogenesis progression cholestatic disease, placing NRs at forefront approaches. This includes BA activated such farnesoid-X receptor (FXR) peroxisome proliferator-activated receptors, respectively, high affinity ligands targeting specific or multiple isoforms have been developed. Moreover, liver-specific thyroid hormone beta 1 complete spectrum available NR-targeted drugs. Apart from FXR ligands, signalling mimetics FXR-activated fibroblast growth factor 19, modulation their enterohepatic circulation through uptake inhibitors in hepatocytes enterocytes, derivatives undergoing cholehepatic shunting (instead circulation). Other approaches more directly target inflammation and/or critical events progression. Combination strategies synergistically disturbances, may ultimately necessary successful treatment complex multifactorial disorders.

Язык: Английский

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Exosomes derived from human adipose mesenchymal stem cells ameliorate hepatic fibrosis by inhibiting PI3K/Akt/mTOR pathway and remodeling choline metabolism

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Янв. 25, 2023

Liver fibrosis is a chronic liver disease with the presence of progressive wound healing response caused by injury. Currently, there are no approved therapies for fibrosis. Exosomes derived from human adipose mesenchymal stem cells (hADMSCs-Exo) have displayed prominent therapeutic effect on diseases. However, few studies evaluated hADMSCs-Exo in and cirrhosis, its precise mechanisms action remain unclear. Herein, we investigated anti-fibrotic efficacy vitro vivo, identified important metabolic changes detailed mechanism through transcriptomic metabolomic profiling. We found could inhibit proliferation activated hepatic stellate aggravating apoptosis arresting G1 phase, effectively inhibiting expression profibrogenic proteins epithelial-to-mesenchymal transition (EMT) vitro. Moreover, it significantly block collagen deposition EMT process, improve function reduce inflammation cirrhosis mice model. The omics analysis revealed that key anti-hepatic was inhibition PI3K/AKT/mTOR signaling pathway affecting metabolites lipid metabolism, mainly regulating choline metabolism. CHPT1 facilitated formation maintenance vesicular membranes. Thus, our study indicates can attenuate cell activation suppress progression fibrosis, which holds significant potential use as extracellular nanovesicles-based therapeutics treatment possibly other intractable

Язык: Английский

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A comprehensive review on the emerging role of long non-coding RNAs in the regulation of NF-κB signaling in inflammatory lung diseases

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 253, С. 126951 - 126951

Опубликована: Сен. 19, 2023

Язык: Английский

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Long Noncoding RNA H19 Contributes to Cholangiocyte Proliferation and Cholestatic Liver Fibrosis in Biliary Atresia

Hepatology, Год журнала: 2019, Номер 70(5), С. 1658 - 1673

Опубликована: Май 7, 2019

Biliary atresia (BA) is a neonatal liver disease featuring cholestasis and severe fibrosis (LF). Despite advances in the development of surgical treatment, lacking an early diagnostic marker intervention LF invariably leads to death from end-stage years life. We previously reported that knockout sphingosine 1-phosphate receptor 2 (S1PR2) protected mice bile duct ligation (BDL)-induced cholangiocyte proliferation LF. Our recent studies further showed both hepatic serum exosomal long noncoding RNA H19 (lncRNAH19) levels are correlated with cholestatic injury multidrug resistance (Mdr2

Язык: Английский

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The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

Seminars in Liver Disease, Год журнала: 2019, Номер 40(01), С. 034 - 048

Опубликована: Сен. 19, 2019

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology PBC remains unknown and pathogenesis features immune-mediated injury, alongside the consequences cholestasis. strongly associated with loss immune tolerance against mitochondrial antigens subsequent presence an articulated immunologic response that involves both humoral cellular responses. Both environmental factors genetic variants increase susceptibility. Biliary epithelial cells have often been considered passive target attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, deoxyribonucleic acid damage recognized play active role PBC. This review highlights discusses most relevant pathogenetic mechanisms PBC, focusing on key lead onset cholestasis activation.

Язык: Английский

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LncSEA: a platform for long non-coding RNA related sets and enrichment analysis

Nucleic Acids Research, Год журнала: 2020, Номер 49(D1), С. D969 - D980

Опубликована: Сен. 30, 2020

Abstract Long non-coding RNAs (lncRNAs) have been proven to play important roles in transcriptional processes and various biological functions. Establishing a comprehensive collection of human lncRNA sets is urgent work at present. Using reference sets, enrichment analyses will be useful for analyzing lists interest submitted by users. Therefore, we developed database, called LncSEA, which aimed document large number available resources provide annotation lncRNAs. LncSEA supports &gt;40 000 across 18 categories 66 sub-categories, covers over 50 We not only collected based on downstream regulatory data sources, but also identified regulated upstream transcription factors (TFs) DNA elements integrating TF ChIP-seq, DNase-seq, ATAC-seq H3K27ac ChIP-seq data. Importantly, provides associated with regulators targets. In summary, powerful platform that variety types users, annotations analyses. The database freely accessible http://bio.liclab.net/LncSEA/index.php.

Язык: Английский

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The Roles and Mechanisms of lncRNAs in Liver Fibrosis

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(4), С. 1482 - 1482

Опубликована: Фев. 21, 2020

Many studies have revealed that circulating long noncoding RNAs (lncRNAs) regulate gene and protein expression in the process of hepatic fibrosis. Liver fibrosis is a reversible wound healing response followed by excessive extracellular matrix accumulation. In development liver fibrosis, some lncRNAs diverse cellular processes acting as competing endogenous (ceRNAs) binding proteins. Previous investigations demonstrated overexpression such H19, maternally expressed 3 (MEG3), growth arrest-specific transcript 5 (GAS5), Gm5091, NR_002155.1, HIF 1alpha-antisense RNA 1 (HIF1A-AS1) can inhibit progression Furthermore, upregulation several [e.g., nuclear paraspeckle assembly (NEAT1), hox antisense (Hotair), liver-enriched fibrosis-associated lncRNA1 (lnc-LFAR1)] has been reported to promote This review will focus on functions mechanisms lncRNAs, lncRNA transcriptome profile main involved signalling pathways provides insight into screening therapeutic diagnostic markers

Язык: Английский

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Long non-coding RNA PVT1 encapsulated in bone marrow mesenchymal stem cell-derived exosomes promotes osteosarcoma growth and metastasis by stabilizing ERG and sponging miR-183-5p

Aging, Год журнала: 2019, Номер 11(21), С. 9581 - 9596

Опубликована: Ноя. 7, 2019

Exosomes secreted by bone marrow mesenchymal stem cells (BMSCs) promote osteosarcoma cell proliferation and migration, while the underlying mechanism remains unknown.Since long non-coding RNA PVT1 has been reported to be upregulated in contributes its growth metastasis, we aim investigate whether BMSC-derived exosomes metastasis via transporting into cells.The expression was markedly higher than that cell-derived exosomes.The co-culturing of (Saos-2, MG-63, MNNG/HOS lines) significantly raised direct binding between oncogenic protein ERG confirmed using immunoprecipitation pull-down assays, transported promotes migration inhibiting degradation ubiquitination ERG.PVT1 also increased through sponging miR-183-5p.In summary, our findings indicated encapsulate PVTl transport it cells, tumor promoting cells.These data provide a novel insight affecting progression.

Язык: Английский

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Cholangiocyte-Derived Exosomal lncRNA H19 Promotes Macrophage Activation and Hepatic Inflammation under Cholestatic Conditions

Cells, Год журнала: 2020, Номер 9(1), С. 190 - 190

Опубликована: Янв. 11, 2020

Activation of hepatic macrophages represents the critical driving force to promote cholestatic liver injury. Exosomes, as important small extracellular vesicles released by almost all types cells, contribute intercellular communication. We previously reported that cholangiocyte-derived exosomal long noncoding RNA (lncRNA) H19 plays a vital role in disrupting bile acid homeostasis hepatocytes and promoting activation stellate cells (HSCs). Exosomal derived from cholangiocytes was rapidly taken up Kupffer cells. However, mechanistic links between lncRNA macrophage-driven inflammation cholestasis remain unclear. Here, we level closely correlated with macrophage fibrosis both Mdr2-/- duct ligation (BDL) mouse models, well human primary sclerosing cholangitis (PSC) biliary (PBC) patients. significantly induced expression secretion chemokine (C–C motif) ligand 2 (CCL-2) interleukin 6 (IL-6) H19-enriched exosomes enhanced M1 polarization promoted recruitment differentiation bone marrow-derived macrophages, which were inhibited CCL-2 pharmacological inhibitor. In conclusion, Cholangiocyte-derived played activation, differentiation, chemotaxis through CCL-2/CCR-2 signaling pathways, represent therapeutic target for diseases.

Язык: Английский

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