Construction of a visualized liver-targeting siRNA delivery system

Abstract

A visualized liver-targeting small-interfering RNA (siRNA) delivery carrier, glycyrrhetinic acid-modified lipid-[poly(aspartate-graft-polyethyleneimine)]-modified superparamagnetic nanoparticles (GLPPS), was prepared for focus on improving the siRNA delivery efficiency and diagnostic capability for hepatocellular carcinoma. Agarose gel electrophoresis, cytotoxicity, and in vitro gene silencing experiments were conducted to determine the optimal carrier formulation. The results showed that the best formulation of the carrier was a weight ratio of LPPS to siRNA of 30:1 and a molar ratio of LPPS to DSPE-PEG-GA of 65:3. Prussian blue staining and in vitro magnetic resonance imaging (MRI) experiments further confirmed that GLPPS had a significant liver-targeting effect. The carrier's biocompatibility was tested both in vitro and in vivo, and the results showed no hemolysis or morphological changes of erythrocytes when the carrier was incubated with rabbit blood cells. Following injection of GLPPS into the tail vein of mice, the hematoxylin and eosin staining of the liver, spleen, and kidney showed normal tissue morphology with no inflammation or injury. Taken together, these results indicated that GLPPS is a safe drug carrier. In vivo MRI showed that GLPPS significantly reduced tumor signal intensity and improved MRI contrast. In conclusion, GLPPS may be a promising liver-targeting siRNA delivery and MRI monitoring carrier.