A ROS-Responsive Self-Assembly Driven by Multiple Intermolecular Interaction Enhances Tumor-Targeted Chemotherapy

Abstract To develop a drug carrier sensitive to reactive oxygen species (ROS), a nanocomplex (NCs) based on sulfuric hyaluronic acid (sHA)-anthocyanin (ATC) was developed. Doxorubicin (DOX) is loaded into the sHA-ATC NCs (AD@sHA) through intermolecular π-π stacking and hydrophobic interactions. AD@sHA can be prepared in aqueous phase by simple mixing method. In AD@sHA, DOX content and load efficiency are high. Compared with D@sHA (without ATC), the ROS-ATC co-mediated responsive degradation and drug release of AD@sHA was confirmed. In addition, AD@sHA also improved apoptosis of CD44+ colon cancer HT29 cells. HT29 tumor-bearing mice model was used to confirm the role of AD@SHA in targeted tumor therapy. The results showed that AD@SHA could optimize the biodistribution of DOX. These data, from tumor volume and TUNEL analysis, observed the delay of tumor growth and apoptosis of cancer cells. Even more exciting is that AD@sHA significantly reduces the myelosuppression of DOX. This study means that AD@sHA has a better effect on chemotherapy for CD44-positive tumors.