Development of glycyrrhizin-conjugated, chitosan-coated, lysine-embedded mesoporous silica nanoparticles for hepatocyte-targeted liver tissue regeneration

Abstract

Mesoporous silica nanoparticles (MSNs) are solid materials possessing a honeycomb-like porous structure and hundreds of empty channels. Developed recently, they are regarded as an efficient drug carrier in the targeted drug delivery system (TDDS). However, most TDDS designs aim to kill tumor cells, and there are fewer related reports about the cell-targeted strategy for enhancing the function of targeted cells. In this study, we applied MSNs to carry lysine for hepatocyte cultures because lysine has been proved to enhance cell mitosis. Moreover, MSNs were encapsulated with chitosan (CS) to enhance the biocompatibility, and glycyrrhizin (GL) was conjugated to MSNs to target hepatocytes. The results showed that (1) MSNs had no cytotoxicity to the hepatocytes in a low concentration (<0.1 mg/mL); (2) the albumin synthesis in hepatocyte cultures with 0.1 mg/mL of lysine increased to a level 30% higher than that in the control; (3) the maximum loading capacity of lysine on MSNs, CS-MSNs, and GL-CS-MSNs was 80%, 70% and 70%, respectively; (4) MSN particles revealed a negative zeta potential of -31.8 mV compared to the CS-MSNs and GL-CS-MSNs, which showed highly positive zeta potentials of 48.9 mV and 34.4 mV, respectively. The average particle size of GL-CS-MSNs and CS-MSNs was relatively larger than that of MSNs (246 nm, 222 nm and 148 nm, respectively); (5) Glycyrrhizin-conjugated, chitosan-coated, lysine-embedded MSNs (GL-CS-ML) were mainly found in hepatocytes; (6) GL-CS-ML enhanced hepatic functions in 7 d of cultures. In conclusion, GL-CS-ML may have a high potential in hepatocyte-targeted research in the near future.