Doxorubicin-loaded micelles with high drug-loading capacity and stability based on zwitterionic oligopeptides

To simplify preparation process and increase the drug-loading capacity of antitumor nanodrugs, doxorubicin-loaded micelles based on zwitterionic oligopeptides were fabricated through two step reactions in mild conditions. Zwitterionic oligopeptides Glu-Lys-Cys-Glu-Lys (EKCEK) were reacted with methacrylohydrazide (MAH) by click reaction, the product was further conjugated with doxorubicin (Dox) to form amphipathic molecules, and finally the amphipathic molecules self-assembled into doxorubicin-loaded micelles (EKCEK-Dox) in deionized water. TEM and DLS results showed that the EKCEK-Dox micelles were of regular sphere, and the mean diameter of the prepared micelles was approximate 70 nm. The drug-loading capacity of the prepared micelles was up to 44.6%, and the micelles were very stable in PBS solution. In vitro antitumor experiment showed that the EKCEK-Dox micelles had significant inhibition efficacy on MCF-7 cells, which was much better than the clinical antitumor drug (Doxil®). The IC50 of the EKCEK-Dox micelles (5.6 µg Dox equiv./mL) was significantly lower than Doxil (8.9 µg Dox equiv./mL). Therefore, the drug delivery system based on zwitterionic oligopeptides will be a promising strategy for cancer chemotherapy.