Theranostic Quercetin Nanoparticle for Treatment of Hepatic Fibrosis

Zhang, Qiang; Xu, Dan; Guo, Qisen; Shan, Wenjun; Yang, Jun; Lin, Tongtong; Ye, Shefang; Xi, Zhou; Ge, Yunshan; Bi, Shengli; Ren, Lei

doi:10.1021/acs.bioconjchem.9b00631

Cited by 29 publications

(18 citation statements)

References 31 publications

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“…Hence, these cells play a pivotal role in the pathogenesis of liver fibrosis. The development of liver fibrosis management is strongly supported by magnetic nanoparticles-based therapy [65,66,67]. Currently, most liver fibrosis treatment is based on iron oxide nanoparticles [68].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Fe3O4/Ag nanohybrid ferrofluids and their applications as antimicrobial and antifibrotic agents

Taufiq

Saputro

Susanto

et al. 2020

Heliyon

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To date, the search for creating stable ferrofluids with excellent properties for biomedical application is one of the challenging scientific and practical investigations. In this study, novel Fe 3 O 4 /Ag nanohybrid ferrofluids from iron sand were synthesized using a double-layer method. The Fe 3 O 4 /Ag nanocomposites exhibited stable crystallite sizes of 11.8 12.1 nm and 36.8-37.2 nm for Fe 3 O 4 and Ag, respectively. The lattice parameters of the spinel structure Fe 3 O 4 and face-centered cubic Ag were respectively 8.344 Å and 4.091 Å. With increasing Ag amount, the crystallite phase of Ag in the nanocomposites increased from 40.2% to 77.2%. The XPS results confirmed that Fe 3 O 4 /Ag nanocomposites were successfully prepared, where Fe 3 O 4 mixed well with Ag via strong ionic bonding. The FTIR results confirmed the presence of Fe 3 O 4 /Ag, oleic acid, and dimethyl sulfoxide as the filler, first layer, and second layer, respectively. The as-prepared ferrofluids exhibited superparamagnetic behavior, where the saturation magnetization decreased with increasing Ag content. The Fe 3 O 4 /Ag nanohybrid ferrofluids exhibited excellent antimicrobial performance against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans. More importantly, the Fe 3 O 4 /Ag nanohybrid ferrofluids decreased the progression of liver fibrosisrelated inflammation and fibrogenic activity on hepatic stellate cells.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Fe3O4/Ag nanohybrid ferrofluids and their applications as antimicrobial and antifibrotic agents

Taufiq

Saputro

Susanto

et al. 2020

Heliyon

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“…These nanocages effectively prevented the HSC proliferation and their activation in vitro. This study shows that multifunctional αvβ3-directed NPs could deliver quercetin to the activated HSCs [36]. Germacrone (GMO), a major bioactive component of Curcuma zedoaria, and miR-29b, an antifibrotic miRNA encapulated into nanoparticles based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA), were developed with cyclical RGD peptides (231.2 nm size) for an active ligand to integrin αvβ3 binding.…”

Section: Nanotargeting Of Activated Hsc Surface Proteins and Signalingmentioning

confidence: 99%

Novel Nano-Based Drug Delivery Systems Targeting Hepatic Stellate Cells in the Fibrotic Liver

Ezhilarasan

Thangavelu

RautBiond

2021

Journal of Nanomaterials

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Hepatic stellate cells (HSCs) exist in the liver’s perisinusoidal space, are phenotypically activated, and acquire myofibroblast-like phenotype. This phenotypic transformation is accountable for the accumulation and production of various extracellular matrix (ECM) proteins, involving different fibril-forming collagens in the perisinusoidal space, producing altered hepatic function and portal hypertension and increased vascular resistance, fibrosis, cirrhosis, and hepatocellular carcinoma. The activated HSCs/myofibroblasts are principal collagen-producing cells in the damaged liver. Therefore, fibrosis treatments are often targeting HSCs. HSCs store most of the total body’s retinol in their cytoplasm, and hence, antifibrotic nanomedicines are often targeted with vitamin A decoration. Vitamin A-decorated nanomedicines with siRNAs for transforming growth factor-beta, collagen, and connective tissue growth factors target to inhibit fibrogenesis and the ECM-associated gene expressions, leading to fibrosis regression. Similarly, a variety of miRNAs play pro- and antifibrotic function. In the fibrotic liver, the profibrotic miRNAs are targeted with their respective antagomir and the antifibrotic miRNAs are targeted with their respective agomirs along with HSC-specific nanodecoration. These miRNA treatments reduce fibrogenesis by downregulation of ECM-related gene expressions. However, liver fibrosis is caused by the upregulation of a different type of profibrotic signaling pathways associated with ECM accumulation in the fibrotic liver. Therefore, specific gene silencing by siRNAs or targeting particularly miRNA may also not effectively reduce fibrosis to a greater extent. However, nanodecoration of a drug is useful to deliver drugs into activated HSCs in the injured liver. Therefore, the aim of this review is to focus on targeted drug delivery towards activated HSCs in the persistently damaged liver.

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“…Nodes with a degree greater than or equal to two-fold median degree values (=6) for all nodes in the network were selected as the core active ingredients ( n = 21, Supplementary Table S8 ) and core targets ( n = 19, Supplementary Table S9 ) of SNS and used to establish the core component-target network ( Figure 3C ). Interestingly, all the core active ingredients with the top 5 degree values (quercetin, liquiritigenin, luteolin, puerarin, saikosaponin A) have been shown to reverse the occurrence and development of liver fibrosis through diverse pathways ( Li et al, 2015 ; Chen et al, 2017 ; Hou et al, 2018 ; Lee et al, 2019 ; Zhang Q. et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Network Pharmacological Analysis and Experimental Validation of the Mechanisms of Action of Si-Ni-San Against Liver Fibrosis

et al. 2021

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Background: Si-Ni-San (SNS), a commonly used traditional Chinese medicine (TCM) formula, has potency against liver diseases, such as hepatitis and non-alcoholic fatty liver disease (NAFLD). However, the therapeutic efficacy and pharmacological mechanisms of action of SNS against liver fibrosis remain largely unclear.Methods: A carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was adopted for the first time to investigate the beneficial effects of SNS on liver fibrosis. The potential mechanisms of action of SNS were explored using the network pharmacology-based strategy and validated with the aid of diverse assays.Results: SNS treatment reduced collagen and ECM deposition, downregulated fibrosis-related factor (hyaluronic acid and laminin) contents in serum, maintained the morphological structure of liver tissue, and improved liver function in the liver fibrosis model. Based on network pharmacology results, apoptosis, inflammation and angiogenesis, together with the associated pathways (including VEGF, TNF, caspase, PPAR-γ and NF-κB), were identified as the mechanisms underlying the effects of SNS on liver fibrosis. Further in vivo experiments validated the significant mitigatory effects of SNS on inflammatory infiltration and pro-inflammatory cytokine contents (IFNγ, IL-1β and TGF-β1) in liver tissues of mice with liver fibrosis. SNS suppressed pathologic neovascularization as well as levels of VEGFR1, VEGF and VEGFR2 in liver tissues. SNS treatment additionally inhibited hepatic parenchyma cell apoptosis in liver tissues of mice with liver fibrosis and regulated apoptin expression while protecting L02 cells against apoptosis induced by TNF-α and Act D in vitro. Activation of hepatic stellate cells was suppressed and the balance between MMP13 and TIMP1 maintained in vitro by SNS. These activities may be associated with SNS-induced NF-κB suppression and PPAR-γ activation.Conclusion: SNS effectively impedes liver fibrosis progression through alleviating inflammation, ECM accumulation, aberrant angiogenesis and apoptosis of hepatic parenchymal cells along with inhibiting activation of hepatic stellate cells through effects on multiple targets and may thus serve as a novel therapeutic regimen for this condition.

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Theranostic Quercetin Nanoparticle for Treatment of Hepatic Fibrosis

Cited by 29 publications

References 31 publications

Synthesis of Fe3O4/Ag nanohybrid ferrofluids and their applications as antimicrobial and antifibrotic agents

Synthesis of Fe3O4/Ag nanohybrid ferrofluids and their applications as antimicrobial and antifibrotic agents

Novel Nano-Based Drug Delivery Systems Targeting Hepatic Stellate Cells in the Fibrotic Liver

Network Pharmacological Analysis and Experimental Validation of the Mechanisms of Action of Si-Ni-San Against Liver Fibrosis

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