Polymeric nanocarriers have been
extensively used in medicinal
applications for drug delivery. However, intravenous nanocarriers
circulating in the blood will be rapidly cleared from the mononuclear
macrophage system. The surface physicochemical characterizations of
nanocarriers are the primary factors to determine their fate in vivo,
such as evading the reticuloendothelial system, exhibiting long blood
circulation times, and accumulating in the targeted site. In this
work, we develop a series of polyurethane micelles containing segments
of an anionic tripeptide, hydrophilic mPEG, and disulfide bonds. It
is found that the long hydrophilic mPEG can shield the micellar surface
and have a synergistic effect with the negatively charged tripeptide
to minimize macrophage phagocytosis. Meanwhile, the disulfide bond
can rapidly respond to the intracellular reduction environment, leading
to the acceleration of drug release and improvement of the therapeutic
effect. Our results verify that these anionic polyurethane micelles
hold great potential in the development of the stealth immune system
and controllable intracellular drug transporters.