Zwitterionic Targeting Doxorubicin-Loaded Micelles Assembled by Amphiphilic Dendrimers with Enhanced Antitumor Performance

Chemotherapy is the main method of treating malignant tumors in clinical treatment. However, the commonly used chemo-therapeutic drugs have the disadvantages of high biological toxicity, poor water solubility, low targeting ability, and high side effects. Zwitterionic micelles assembled by amphiphilic dendrimers modified with zwitter-ionic groups and targeting ligand should largely overcome these shortcomings. Herein, the zwitterionic group and targeting peptide c(RGDfC) were modified on the surface of generation 2 poly(propylene imine) dendrimers (G2 PPI), which was conjugated with hydrophobic N-(2-mercaptoethyl) oleamide to form amphiphilic dendrimers (PPIMYRC). PPIMYRC self-assembled into micelles with doxorubicin (DOX) loaded in the interior of micelles to prepare DOX-loaded micelles (PPIMYRC-DOX micelles). The PPIMYRC-DOX micelles had great stability in fibrinogen and pH-responsive drug release. Furthermore, PPIMYRC-DOX micelles had higher cellular uptake rates than free DOX, resulting in higher cytotoxicity of PPIMYRC-DOX micelles than that of free DOX. More importantly, PPIMYRC-DOX micelles inhibited tumors much better than free DOX. The tumor inhibition rate of PPIMYRC-DOX micelles was as high as 93%. Taken together, PPIMYRC-DOX micelles were assembled by amphiphilic dendrimers with the zwitterionic and targeting groups, which enhanced the therapeutic effect of DOX and reduced its side effects. The prepared targeting nanodrug has great potential for further application in antitumor therapy.

Automated summary

Chemotherapy is the main method of treating malignant tumors, but commonly used drugs have high toxicity, poor solubility, low targeting ability, and high side effects. In this study, zwitterionic micelles assembled by modified amphiphilic dendrimers showed great stability and controlled drug release. Moreover, these micelles had higher cellular uptake rates and cytotoxicity, resulting in better tumor inhibition compared to free drugs. Therefore, the prepared targeting nanodrug has great potential for antitumor therapy.