Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-
DMMA) were constructed with a
tumor-targeting
ligand (
hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic
anhydride,
DMMA) on the other side. The drug release of HA-JMSN/DOX-
DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-
DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-
DMMA involved the
clathrin-mediated endocytosis (HA) and the micropinocytosis (
DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and
tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-
DMMA in
tumor was enhanced significantly. The antitumor
therapy study in vivo showed that HA-JMSN/DOX-
DMMA inhibited
tumor growth and improved the survival rate of
tumor-bearing mice effectively. In general, HA-JMSN/DOX-
DMMA could take the synergistic effect of active targeting and charge reversal to deliver
drug in
tumor cells and kill them efficiently, which was a promising antitumor nanodrug.