Development of a peptide-modified siRNA nanocomplex for hepatic stellate cells

Zhao, Zhen; Li, Yuanke; Jain, Akshay; Chen, Zhijin; Líu, Hao; Jin, Wei; Cheng, Kun

doi:10.1016/j.nano.2017.08.017

Cited by 46 publications

(48 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the invasion study, the Transwell chamber was precoated with 50 μg of Matrigel, and 2 × 10 5 cells were seeded in the precoated Transwell with serum-free DMEM. After 6 hours for the migration assay and 24 hours for the invasion assay, the migrated cells were fixed with 10% paraformaldehyde, stained with 0.05% crystal violet, and counted as previously described ( 29 , 40 ).…”

Section: Methodsmentioning

confidence: 99%

“…The Cy5-labeled IKBKE siRNA (50 nM) was used to form the siRNA nanocomplex. Two, 4, and 6 hours after transfection, the cells were treated with 40 μM heparin, and cellular uptake was measured using a FACS II flow cytometer (BD Instrument, NJ) ( 40 ). Confocal microscopy was performed 2 and 6 hours after transfection.…”

Section: Methodsmentioning

confidence: 99%

“…For Western blot assays, the cells were first transfected with the IKBKE siRNA in Opti-MEM for 24 hours, replaced with fresh medium, and incubated for another 24 hours. Total proteins were isolated, and the silencing activity was quantified using Western blot as previously reported (3,40).…”

Section: Synthesis Of Cholesterol-peptidementioning

confidence: 99%

See 2 more Smart Citations

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer

Zhao

Líu

et al. 2020

Sci. Adv.

Self Cite

View full text Add to dashboard Cite

IKBKE is an oncogene in triple-negative breast cancer (TNBC), and we demonstrate that IKBKE small interfering RNA (siRNA) inhibits the proliferation, migration, and invasion of TNBC cells. Despite the recent success of siRNA therapeutics targeting to the liver, there still remains a great challenge to deliver siRNAs to solid tumors. Here, we report a hybrid nanocomplex to co-deliver the IKBKE siRNA and cabazitaxel to TNBC to achieve an optimal antitumor effect. The nanocomplex is modified with hyaluronic acid to target CD44 on TNBC cells. The nanocomplex shows higher cellular uptake and better tumor penetration of the encapsulated cargos. The nanocomplex also exhibits high tumor accumulation and antitumor activity in an orthotopic TNBC mouse model. Encapsulation of cabazitaxel in the nanocomplex enhances the activity of the IKBKE siRNA. The hybrid nanocomplex provides a novel and versatile platform for combination therapies using siRNAs and chemotherapy.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer

Zhao

Líu

et al. 2020

Sci. Adv.

Self Cite

View full text Add to dashboard Cite

show abstract

“…It was shown that patients with low IGF2R expression had poorer prognosis after chemotherapy. Cholesterol amongst other ligands is known to bind IGF2R for delivery of Poly (rC)-Binding Protein 2 (PCBP2) siRNA to hepatic stellate cells (HSCs) [119]. These findings suggest that selected miRNAs (miR-128 and miR-223) may be potential anti-cancer drug resistance targets.…”

Section: Hsa-mir-128 and Hsa-mir-223 Potentially Regulate Genes Involmentioning

confidence: 99%

microRNAs targeting cellular cholesterol: implications for combating anticancer drug resistance

Monchusi

Kaur

2020

Genes Cancer

View full text Add to dashboard Cite

Over sixty percent of all mammalian protein-coding genes are estimated to be regulated by microRNAs (miRNAs), and unsurprisingly miRNA dysregulation has been linked with cancer. Aberrant miRNA expression in cancer cells has been linked with tumourigenesis and drug resistance. In the past decade, increasing number of studies have demonstrated that cholesterol accumulation fuels tumour growth and contributes to drug resistance, therefore, miRNAs controlling cholesterol metabolism and homeostasis are obvious hypothetical targets for investigating their role in cholesterol-mediated drug resistance in cancer. In this review, we have collated published evidences to consolidate this hypothesis and have scrutinized it by utilizing computational tools to explore the role of miRNAs in cholesterol-mediated drug resistance in breast cancer cells. We found that hsa-miR-128 and hsa-miR-223 regulate genes mediating lipid signalling and cholesterol metabolism, cancer drug resistance and breast cancer genes. The analysis demonstrates that targeting these miRNAs in cancer cells presents an opportunity for developing new strategies to combat anticancer drug resistance.

show abstract

“…Curcumin, a diarylheptanoid obtained from turmeric, suppresses HSC activation by inhibiting the TGF-β signaling and downregulating the expression of tea, also exhibit anti-fibrotic effects in animals. In addition, it has been shown that siRNAs have high efficiency and specificity for liver 26,27 fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticles Targeting Hepatic Stellate Cells for the Treatment of Liver Fibrosis

Hu¹,

Lee²,

Luo³

2019

Eng. Sci.

View full text Add to dashboard Cite

Liver fibrosis is a scarring process that can progress to cirrhosis, the primary cause for hepatocellular carcinoma. Although various anti-fibrotic agents have been explored for liver fibrosis treatment, their clinical applications have been limited due to insufficient delivery of the agents to target cells and toxicity. Hepatic stellate cells (HSC) play key roles in the development of liver fibrosis because they produce extracellular matrix proteins, such as collagens, when activated upon liver injury. Therefore, surface engineering of organic nanoparticles (such as liposomes, polymeric, and lipid nanoparticles) with ligands specific to the overexpressed receptors secreted by activated HSC during hepatic fibrogenesis has been exploited in the last decade to develop effective approaches to reverse liver fibrosis. Passive targeting has also been explored as a potential strategy to deliver anti-fibrotic agents to activated HSC through systemic administration of non-ligand nanoparticles, including both organic (polymeric and lipid) and inorganic (mesoporous silica, cerium oxide and silver) nanoparticles. This review focuses on the most recent literatures concerning different types of nanoparticles for liver fibrosis treatment via HSC-targeting delivery of various anti-fibrotic agents by the two strategies aforementioned, with special emphasis on their therapeutic mechanisms and biological efficacies at both cellular and the whole body levels.

show abstract

Development of a peptide-modified siRNA nanocomplex for hepatic stellate cells

Cited by 46 publications

References 46 publications

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer

Co-delivery of IKBKE siRNA and cabazitaxel by hybrid nanocomplex inhibits invasiveness and growth of triple-negative breast cancer

microRNAs targeting cellular cholesterol: implications for combating anticancer drug resistance

Nanoparticles Targeting Hepatic Stellate Cells for the Treatment of Liver Fibrosis

Contact Info

Product

Resources

About