Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy

Ji, De; Wang, Qiaohan; Zhao, Qi; Tong, Huangjin; Yu, Mengting; Wang, Meng; Lu, Tulin; Jiang, Chengxi

doi:10.1186/s12951-020-00645-y

Cited by 30 publications

(24 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This nanoparticle system efficiently internalized into HSCs via αvβ3-mediated endocytosis. GMO and miR-29b inhibit the proliferation of activated HSCs and collagen 1 expression, and in vivo, this nanoparticle system ameliorated CCl 4 -induced liver fibrosis in mice [37].…”

Section: Nanotargeting Of Activated Hsc Surface Proteins and Signalingmentioning

confidence: 88%

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

Ezhilarasan

Thangavelu

RautBiond

2021

Journal of Nanomaterials

View full text Add to dashboard Cite

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.

show abstract

Section: Nanotargeting Of Activated Hsc Surface Proteins and Signalingmentioning

confidence: 88%

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

Ezhilarasan

Thangavelu

RautBiond

2021

Journal of Nanomaterials

View full text Add to dashboard Cite

show abstract

“…Modern research has shown that furanodienone, . Germacrone not only has protective effect on acute liver injury but also inhibits the proliferation and promotes apoptosis of liver cancer cells, breast cancer cells, lung cancer cells, and glioma cells [17,18]. Chen et al found that furanodienone, a diene-type sesquiterpene isolated from the rhizomes of Rhizoma Curcumae, exhibited a potential cytotoxic effect on temozolomide-(TMZ-) resistant GBM cells in vitro by inhibiting CSPG4 and related signalling pathways [19].…”

Section: Discussionmentioning

confidence: 99%

Study on Quality Standards and Hepatoprotective Effect of Curcuma phaeocaulis Radix

Chen

Liao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Curcuma phaeocaulis Radix (Lüsiyujin) is a mainstream variety of Curcumae Radix cultivated in Sichuan for more than 900 years, but its broader utility is limited by a lack of quality control and pharmacodynamic research. We used the Chinese Pharmacopoeia, 2015 edition, to guide the determination of germacrone and furanodienone content in extracts. We established an animal model of Qi stagnation and blood stasis in a clinical context. Pathological changes in liver function indexes were evaluated to investigate the hepatoprotective effect of Lüsiyujin. In 20 extraction batches of Lüsiyujin, ethanol extracts yielded 9.22%–15.01%, average 12.03%. The germacrone content was 0.003%–0.011% (average 0.0069%), and the furanodienone content was 0.090%–0.478% (average 0.201%). Compared with the control group, the model rats exhibited functional liver damage. Serum markers of liver function varied after treatment with Lüsiyujin, but significant effects were observed with alanine aminotransferase and total bile acid. This study demonstrates a simple method of quality control for Lüsiyujin. The study also demonstrated that Lüsiyujin inhibits hepatocyte damage and regulates the excretion and secretion of hepatic bile. Our findings provide a theoretical basis for the formulation of quality standards, clinical application, and resource development for the utilisation of Lüsiyujin.

show abstract

“…HE, Masson, and Sirius‐red staining were performed as previous reported 21 . Fresh heart tissues were fixed in 4% paraformaldehyde and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

“…2.5 | hematoxylin-eosin (HE), Masson, and Sirius-red staining HE, Masson, and Sirius-red staining were performed as previous reported. 21 Fresh heart tissues were fixed in 4% paraformaldehyde and embedded in paraffin. Five-micron sections were obtained, deparaffinized, and rehydrated as previously described.…”

Section: Quantitative Real-time Pcr (Qrt-pcr)mentioning

confidence: 99%

LncRNA SOX2OT/Smad3 feedback loop promotes myocardial fibrosis in heart failure

Liao

et al. 2020

IUBMB Life

View full text Add to dashboard Cite

Long noncoding RNA SOX2OT is associated with myocardial fibrosis (MF) in heart failure (HF). This article aims to investigate the role of SOX2OT in MF. We constructed HF mouse models by subcutaneous injection of isoprenaline (ISO). Cardiac fibroblasts (CFs) were treated with ISO to induce MF. Hematoxylin-eosin, Masson, and Sirius-red staining were used to identify myocardial injury and collagen deposition in heart tissues. The relationship among SOX2OT, miR-138-5p, TGF-β1, and Smad3 were evaluated by chromatin immunoprecipitation and luciferase reporter assay. The gene and protein expression were verified by quantitative real-time PCR and western blot. We found that SOX2OT was up-regulated in HF mice and ISO-induced CFs. SOX2OT knockdown reduced myocardial injury and collagen deposition in HF mice. The expression of collagen I, α-SMA, TGF-β1, and p-Smad3 were inhibited by SOX2OT down-regulation in HF mice and ISO-induced CFs. Furthermore, TGF-β1 was a target gene of miR-138-5p and indirectly regulated by SOX2OT. SOX2OT promoted MF in HF by activating TGF-β1/Smad3, and then Smad3 interacted with the SOX2OT promoter and formed a positive feedback loop. In conclusion, our work verifies that SOX2OT/Smad3 feedback loop promotes MF in HF. Thus, SOX2OT is potentially a novel therapeutic target for MF in HF.

show abstract

Co-delivery of miR-29b and germacrone based on cyclic RGD-modified nanoparticles for liver fibrosis therapy

Cited by 30 publications

References 43 publications

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

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

Study on Quality Standards and Hepatoprotective Effect of Curcuma phaeocaulis Radix

LncRNA SOX2OT/Smad3 feedback loop promotes myocardial fibrosis in heart failure

Contact Info

Product

Resources

About