Antibodies
are promising biopharmaceuticals that offer new therapeutic
options for diseases. Since antibodies are membrane impermeable, approaches
that allow immunoglobulin Gs (IgGs) to access intracellular therapeutic
targets would open new horizons in antibody therapies. Lipid nanoparticles
(LNPs) are among the classes of vectors that deliver biopharmaceuticals
into cells. Using liquid droplets formed by IgG and polyglutamate,
we report here a unique approach to forming LNPs containing IgG via
liquid droplets formed in the presence of polyglutamic acid (polyE).
The addition of polyE promoted the formation of smaller LNPs with
cationic lipids than in its absence, and the formed LNPs were much
more efficient in cytosolic IgG delivery and targeting of cellular
proteins. This approach also allows for the encapsulation of intact
IgG without the need for chemical or sequence modification. The intracellularly
delivered IgG retained its target binding ability, as demonstrated
by labeling of nuclear pore complex and HRas-GFP and inhibition of
antiapoptotic cell death by phosphorylated Akt protein in live cells.