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Updated: Jun 18, 2026
On-Chip Octanol-Assisted Liposome Assembly for Bioengineering
Published on: March 17, 2023
Intracellular fate of octaarginine-modified liposomes in polarized MDCK cells
Takahiro Fujiwara1, Hidetaka Akita, Hideyoshi Harashima
1Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Abstract:
Octaarginine (R8)-modified liposomes have been used to deliver therapeutic substances into cells owing to the efficient cellular uptake via macropinocytosis. Recent analyses revealed that R8-modified liposomes are mainly taken up via macropinocytosis, and escape from endosomes efficiently to avoid lysosomal degradation in non-polarized NIH-3T3 cells. In the present study, we evaluated the intracellular fate of R8-modified liposomes in polarized MDCK cells, comparing their trafficking with that of conventional cationic liposomes by confocal laser scanning microscopy (CLSM). In contrast to what occurs in NIH-3T3 cells, R8-modified liposomes are internalized by MDCK cells equally well via clathrin-mediated endocytosis and macropinocytosis. The most salient characteristic in subsequent intracellular trafficking in MDCK cells is that R8-modified liposomes become trapped in the endosomal compartment and subsequently, a portion of them colocalizes with the Golgi apparatus. Similar colocalization with the Golgi apparatus was observed for octalysine (K8)-modified liposomes. In contrast, cationic liposomes were found to colocalize predominantly with lysosomes stained with lysotracker. Collectively, in polarized MDCK cells, cationic peptide-modified liposomes may be subjected to a different sorting pathway from that used for liposomes composed of cationic lipids.
Insights
Octaarginine (R8)-modified liposomes show distinct cellular uptake and trafficking in polarized MDCK cells, unlike in non-polarized cells. These R8 liposomes are internalized via multiple pathways and accumulate in the Golgi apparatus, avoiding lysosomal degradation.
Area of Science:
- Cell biology
- Nanotechnology
- Drug delivery
Background:
- Octaarginine (R8)-modified liposomes facilitate efficient cellular uptake via macropinocytosis.
- Previous studies in non-polarized cells showed R8 liposomes primarily use macropinocytosis and escape endosomes to avoid lysosomal degradation.
Purpose of the Study:
- To investigate the intracellular trafficking of R8-modified liposomes in polarized Madin-Darby canine kidney (MDCK) cells.
- To compare the behavior of R8 liposomes with conventional cationic liposomes in polarized MDCK cells.
Main Methods:
- Confocal laser scanning microscopy (CLSM) was employed to track liposome intracellular fate.
- Polarized MDCK cells were used to model cellular uptake and trafficking dynamics.
- Lysotracker was used to identify lysosomal compartments.
Main Results:
- In polarized MDCK cells, R8-modified liposomes are internalized through both clathrin-mediated endocytosis and macropinocytosis.
- Unlike in non-polarized cells, R8 liposomes in MDCK cells become trapped in endosomes and partially colocalize with the Golgi apparatus.
- Octalysine (K8)-modified liposomes also showed Golgi colocalization, whereas conventional cationic liposomes predominantly localized to lysosomes.
Conclusions:
- Cationic peptide-modified liposomes exhibit unique intracellular trafficking pathways in polarized cells compared to non-polarized cells.
- R8-modified liposomes in polarized MDCK cells follow a distinct sorting pathway, potentially involving the Golgi apparatus and avoiding lysosomal degradation.
- This suggests that cell polarity significantly influences the intracellular fate and delivery potential of peptide-modified liposomes.
