Dual-functionalized Janus Mesoporous Silica Nanoparticles with Active Targeting and Charge Reversal for Synergistic Tumor Targeting Therapy.

Janus nanoparticles with 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 tumor targeting ligand (HA) modified on the one side and charge reversal group (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 was 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 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 synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising anti-tumor nanodrug.

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