Nanoparticles for Creating a Strategy to Stimulate Liver Regeneration.

Abstract

Presently, there is a need in the developing new approaches to stimulate liver regeneration, which would make its recovery more effective after resection. Application of nanoparticles, loaded with small bioactive molecules, with their targeted delivery into the liver is a promising approach. The aim of the investigation is to study the interaction of nanoparticles with various types of hepatic cells on the models of liver slices and primary hepatic cell cultures using the methods of multiphoton microscopy with fluorescence lifetime imaging.

Materials and methods: Nanoparticles have been synthetized from polylactide (PLA), gold (Au), and silicon (SiO₂), and characterized using scanning and transmission electron microscopy. These types of particles were labeled with a fluorescent Cy5 dye for their visualization. Liver slices and a primary hepatocyte culture were used as models for biological testing of nanoparticles. Biodistribution of the nanoparticles in the tissue and cells, their cytotoxicity, and the effect on the cell metabolism were assessed using optical bioimaging methods.

Results: The silicon nanoparticles are accumulated mainly by macrophages, which generate reactive oxygen species in a large amount and impair the native metabolic state of hepatocytes. The gold nanoparticles accumulate in all types of the liver cells but possess a marked toxic effect, which is indicated by the appearance of necrotic and apoptotic cells and a sharp change in the hepatocyte metabolic state. The polylactide nanoparticles accumulate most effectively in the liver cells, preferably in hepatocytes, do not change their native metabolic state, making this type of nanoparticles most promising for creating the bioactive molecule delivery systems to stimulate liver regeneration.