Liposomes injected intravenously into mice associate with liver mitochondria

Area of Science:

• Cell Biology
• Nanotechnology
• Hepatology

Background:

• Liposomes are widely used drug delivery systems.
• Understanding liposome-hepatocyte interactions is crucial for targeted therapies.
• Previous studies suggest varied cellular fates for liposomes.

Purpose of the Study:

• To investigate the in vivo intracellular fate of liposomes in mouse liver.
• To determine the interaction of liposomes with liver cells and organelles post-intravenous injection.

Main Methods:

• Intravenous injection of liposomes encapsulating uranyl acetate or ferritin into mice.
• Transmission electron microscopy (TEM) and freeze-fracture-etching analysis of liver tissues at various time points (20 min, 1 h, 4 h).
• Isolation of hepatocytes via collagenase perfusion for TEM analysis.

Main Results:

• Oligolamellar liposomes were observed to associate with liver mitochondria at all time points.
• An average of 10% of mitochondria showed liposome association at 1 hour post-injection.
• Liposomes were found within cytoplasmic vacuoles in hepatocytes and Kupffer cells, with evidence of phagocytosis and lysosomal degradation.
• Lactosylceramide incorporation into liposomes did not alter their intracellular fate, suggesting plasma membrane interactions are key.

Conclusions:

• Liposomes interact with hepatic mitochondria in vivo.
• Cellular uptake involves cytoplasmic vacuoles, phagocytosis by Kupffer cells, and lysosomal pathways.
• Liposome-plasma membrane interactions, rather than bilayer composition, may dictate initial cellular engagement.