Nanomedicine For Liver Fibrosis Therapy

In recent years,the number of patients with liver cancer is increasing,and liver fibrosis is the main background factor of its occurrence and development.Liver fibrosis is a dynamic and reversible process with self-repairing ability.The reversibility of liver fibrosis provides an effective early window for treatment.However,there is no ideal anti-fibrosis drug in clinical practice.The functional changes of liver microstructural components in the fibrosis microenvironment,especially the complexity of the function of liver macrophage population,are the hotspots and difficulties in current research.In this thesis,nano-drug delivery systems with different characteristics were designed and prepared,and the best nano-drug delivery system was selected for the treatment of liver fibrosis through the study of its interaction with liver microstructure components.The research content of this thesis are as follows:1?We successfully prepared three kinds of lipid-assisted nanocarriers with different charges,and then studied their enrichment effect in liver and distribution in liver microstructure.The results show that the positively charged lipid-assisted nanocarrier(NP^10%DOTAP)has the strongest liver enrichment ability and is easier to achieve liver parenchymal penetration;Negatively charged lipid-assisted nano carriers(NP^10%DOTAP)are the second most abundant in liver,and are more easily taken up by Kupffer cells;Neutral lipid-assisted nanocarriers?NP?have the weakest liver enrichment ability.In the mouse liver fibrosis model,sorafenib-loaded NP^10%DOTAP can better retard the progression of fibrosis,suggesting that NP^10%DOTAP has better drug delivery potential for the treatment of liver disease.2?On the one hand,based on the understanding of the liver microstructure,we prepared carbon quantum dot nanoparticles?CD?with a size of about 23 nm,which can achieve rapid enrichment and slow metabolism in the liver.On the other hand,we successfully prepared Dex bonded carbon quantum dots?CD-Dex?nanoparticles based on the understanding of the liver fibrosis microenvironment.In vivo and in vitro results showed that CD-Dex nanoparticles have more effective inhibition of inflammatory cell infiltration and activation.In the mouse liver fibrosis model,CD-Dex nanoparticles also showed better anti-fibrosis effect.In conclusion,our experimental results have demonstrated the effectiveness of this CD-Dex nanoparticles which design based on liver microstructure and fibrosis microenvironment.Our work provides a new perspective and ideas for designing intelligent nanocarriers and targeted delivery to alleviate liver inflammation and fibrosis.