Antifibrotic and Antioxidant Effects of a Tetrahedral Framework Nucleic Acid-Based Chlorogenic Acid Delivery System

Liver fibrosis, an early stage of cirrhosis, with large number of patients and seriously endangering health, has no viable treatment available currently. In this study, we choose tetrahedral framework nucleic acid nanoparticles as carriers to deliver the polyphenolic monomer chlorogenic acid to the injured liver for the first time. This delivery system has enhanced bioavailability and stability of the chlorogenic acid, laying the foundation for its antifibrotic and antioxidant effects. Our findings show that this delivery approach can reduce fibrosis by down-regulating Smad2/3 phosphorylation, limiting extracellular matrix synthesis, and substantially improving the fibrosis performance of mouse livers and restoring normal liver function; besides, the delivery system can promote reactive oxygen species consumption by upregulating Nrf2, regulating oxidative stress and alleviating multiorgan damage in mice. In general, we created a nanodelivery system of chlorogenic acid associated with liver fibrosis, providing more possibilities for the clinical application of small molecule drugs.