University of Twente Student Theses
Targeting inflammation and fibrosis in liver injury mouse models by modulating microrna-155 expression using passive liver targeting lipid nanoparticles
Tuli, Vishal (2023) Targeting inflammation and fibrosis in liver injury mouse models by modulating microrna-155 expression using passive liver targeting lipid nanoparticles.
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| Abstract: | Chronic liver injuries are a major health risk worldwide and responsible for over 1.2 million deaths globally each year. They can be caused by a variety of etiologies such as alcohol abuse, hepatitis B/C viral infections, unhealthy diet and lifestyle etc. but follow a common progression of hepatocellular damage induced inflammation and fibrosis, leading to cirrhosis and/or hepatocellular carcinoma. Even with a significant burden on healthcare, chronic liver diseases do not have a therapy showing significant benefit in terms of amelioration of inflammation or fibrosis available in the market. The differential expression of miRNAs has been explored as a potential diagnostic tool as well as a therapeutic target in liver diseases. miRNAs are small non-coding RNAs that regulate the expression of mRNAs by binding to their 3’UTR. Of the multiple miRNAs differentially regulated in chronic liver diseases, miRNA-155 is considered as the main inflammation and fibrosis regulator, also known as a master regulator of inflammation. Lipid nanoparticles (LNPs) are one of the best non-viral delivery systems for nucleic acid and were explore for delivering antimiR-155 to the liver as a therapeutic strategy. Three different LNP formulations based on different helper lipids – DSPC, DOPC and DOPE, were engineered and characterized for differences in their physiochemical properties showing variation in zeta potential. None of the LNPs affected the metabolic activity of the cell populations treated with them. They were explored in the context of in vitro cellular uptake specificity in cell lines representing liver populations (RAW264.7, AML12, 3T3 and H5V) and in vivo organ biodistribution, in an acute liver injury mouse model. DSPC LNPs showed the best results in passive targeting of the liver and were employed to deliver antimiR-155 in a therapeutic efficacy study using a semi-chronic liver injury mouse model. The antimiR-155 DSPC LNP therapy showed a trend of amelioration of inflammation and fibrosis as compared to the Negative Control – LNP (NC-LNP) treatment, presenting itself as a promising therapeutic strategy in focus of chronic liver injuries. |
| Item Type: | Essay (Master) |
| Faculty: | TNW: Science and Technology |
| Subject: | 42 biology, 44 medicine |
| Programme: | Biomedical Engineering MSc (66226) |
| Awards: | Cum Laude |
| Link to this item: | https://purl.utwente.nl/essays/97186 |
| Export this item as: | BibTeX EndNote HTML Citation Reference Manager |
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