Exosomes
mediate communication between cells in the body by the incorporation
and transfer of biological materials. To design an artificial liposome,
which would mimic the lipid composition and physicochemical characteristics
of naturally occurring exosomes, we first studied the physicochemical
properties of exosomes secreted from HepG2 cells. The exosome stiffness
obtained by atomic force microscopy was moderate. Some liposomes were
then fabricated to mimic the representative reported lipid composition
of exosomes. Their physicochemical properties and cellular internalization
efficiencies were investigated to optimize the cellular internalization
efficiency of the liposomes. A favorable internalization efficiency
was obtained by incubating HeLa cells with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol (Chol)/1,2-dioleoyl-sn-glycero-3-phospho-l-serine (DOPS) (40/40/20
mol %) liposomes, which have a similar stiffness and zeta potential
to exosomes. A dramatic increase in internalization efficiency was
demonstrated by adding DOPS to simple DSPC/Chol liposomes. We found
that DOPS had a more desirable effect on cellular internalization
than its saturated lipid counterpart, 1,2-distearoyl-sn-glycero-3-phospho-l-serine. Furthermore, it was shown that
the phosphatidylserine-binding protein, T-cell immunoglobulin mucin
protein 4, was largely involved in the intracellular transfer of DSPC/Chol/DOPS
liposomes. Thus, DOPS was a key lipid to provide the appropriate stiffness,
zeta potential, and membrane surface affinity of the resulting liposome.
Our results may help develop efficient drug carriers aiming to internalize
active substances into cells.