The challenge in effective delivery of mRNA has been
a major hurdle
in their development as therapeutics. Herein, we present that the
incorporation of cationic nanogels as the condensing material for
mRNA into liposomes enables stable and enhanced mRNA delivery to cells in vitro. We prepared dextran-based nanogel particles, which
were surface functionalized with oligoarginine peptide (DNPR9) and
complexed with mRNA for incorporation into liposomes (LipoDNPR9).
The use of DNPR9 with the liposomes resulted in enhanced internalization,
as well as a 4-fold increase in transfection of luciferase mRNA when
treated with A549 cells in vitro, compared to control
liposomes. The enhancement in transfection efficiency was also observed
in various cell lines while causing low cytotoxicity. The versatility
of the strategy was also investigated by applying DNPR9 for mRNA condensation
to ionizable lipid particles, which resulted in an ∼55% increase
in transfection. The current development based on nanogel-incorporated
liposomes introduces an effective platform for mRNA delivery, while
the condensation strategy using DNPR9 can be widely applied for various
lipid-based formulations to enhance their efficacy
