Hepatitis B Core Protein Nanocages Loaded With Quercetin For Treatment And MRI Of Hepatic Fibrosis In Rat

Hepatic fibrosis is a compensatory response of the liver after external damage,mainly manifested by excessive deposition of extracellular matrix.In the development of chronic liver disease,liver fibrosis tissue is infiltrated by a large number of inflammatory cells,resulting in hyperproliferation,sclerosis and scarring,liver function disorder,and then develop into cirrhosis,and even induce liver cancer.Research reports have shown that liver fibrosis is pathologically reversible.Although the pathogenesis of liver fibrosis is complex,activation of hepatic stellate cells is a critical step.Integrin ?v?3 expression is significantly up-regulated during the proliferation and migration of activated hepatic stellate cells,and has become a reliable target for targeted therapy of liver fibrosis in recent years.Quercetin is one of the most abundant flavonoids in the human diet.Studies have shown that quercetin can relieve liver oxidative damage,inhibit inflammation,and has significant anti-fibrotic effects.However,quercetin is almost insoluble in water and has poor bioavailability.Therefore,it is of great significance to use nanotechnology to achieve targeted delivery of quercetin.Hepatitis B virus core protein nanocage(HBc NCs)is an excellent carrier protein with good biocompatibility and cell permeability,and its internal and external cage structure can be modified by chemical or genetic engineering.An ideal delivery system for drugs or imaging probes.This study aims to design and construct a novel therapeutic diagnostic nanoformer for MR imaging and treatment of liver fibrosis.The target peptide RGD is displayed on the surface of protein nanocage(HBc NCs)by genetic engineering,and the affinity of RGD and integrin ?v?3 enables the protein nanocage to rapidly target the fibrotic liver.In order to solve the problem of poor water solubility of quercetin,sulfobutylether-?-cyclodextrin(SBE-?-CD)was introduced,and the quercetin was encapsulated by the hydrophobic property of the surface hydrophilic cavity,and then electrostatically adsorbed.The inclusion complex was loaded into the cavity of the RGD-HBc NCs.Rapid targeting of RGD-HBc/QR NCs to study the therapeutic effects of nanoformulations on liver fibrosis.In addition,RGD-HBc/QGd NCs were prepared by encapsulating the prepared contrast agent(quercetin-ruthenium complex,QGd)into protein nanocage using the same strategy to study the MR imaging effect on liver fibrosis.In conclusion,RGD-HBc NCs have the potential to be an integrated reagent for the diagnosis and treatment of liver fibrosis.