Zwitterionic dendrimer self-assembled nanodrugs with high drug loading for enhanced anti-tumor ability

Zwitterionic dendrimers have been used to construct many nanomedicines due to their ability to achieve controlled drug release, but their low drug loading content limits their application in nanodrug delivery. To solve this problem, the surface of second generation polypropylimine (G2 PPI) was modified with mercapturized paclitaxel (PTX-SH) and zwitterionic groups to prepare zwitterionic prodrug molecule (PPIMPC), and then zwitterionic dendrimer self-assembled nanodrugs (PPIMPC-DOX micelles) were prepared by incorporating doxorubicin (DOX) into the micelles. The DOX loading and paclitaxel (PTX) loading in PPIMPC-DOX micelles was 6.7% and 26.2%, respectively, and the total drug loading of PPIMPC-DOX was high to 32.9%. In addition, PPIMPC-DOX micelles showed enhanced cytotoxicity due to improved cell uptake of DOX. More importantly, the inhibition rate of tumor was much higher than free DOX. The zwitterionic property and high drug loading of PPIMPC-DOX micelles enhanced anti-tumor ability of chemotherapeutic drugs. The method of preparation of zwitterionic and high drug loading of nanodrugs shows good application prospects in the future.