pH and hydrogen peroxide dual responsive supramolecular prodrug system for controlled release of bioactive molecules.
Nowadays, cancer is one of the most fatal threatens to human health. By utilizing the differences of cell environment between cancer cells and their normal counterparts as assembly-disassembly triggers, various smart drug nanocarriers have been designed to fight the cancer. Nevertheless, most of them are still not robust enough. One important reason is that they merely focus on a single stimulus. Thus, in order to achieve a better therapeutic effect, constructing multi responsive polymers is of great significance. However, most of multi responsive polymers used, up until now, are mainly based on block polymers synthesized via traditional polymerization methods, which are relatively time-consuming and laborious. Here in this article, a facile strategy preparing smart polymers with dual responsiveness (endosomal pH and over produced H2O2) was proposed and realized by orthogonal assembly of β-CD-hydrazone-DOX and PEG-Fc. The obtained polymers were found to be able to spontaneously assemble into micelles in water, indicating their potential applications as drug nanocarriers. In vitro study revealed that the release of the encapsulated DOX was significantly enhanced by both H2O2 and low pH at 5.0. Furthermore, fluorescence microscopy and flow cytometry analysis showed that the assembled supramolecular prodrug micelles could be internalized into cancer cells. These properties suggested their promising application in cancer therapy.