Sequential drug release for synergistic cancer treatment and immunity promotion

Abstract

Rehabilitation of patients is closely related to immunity improvement, while almost all anticancer drugs kill leukocytes, one kind of important immune cell, to silence the immune system. Therefore, it is particularly important to protect leukocytes in the process of cancer chemotherapy. In this work, a sequential drug release for synergistic cancer treatment and immunity promotion has been constructed. Firstly, hyperbranched glycidol (HPG) was synthesized by cationic ring-opening polymerization. Benefiting from the existence of many hydroxyl end-groups in HPG, the traditional Chinese medicine norcantharidin (NCTD) anhydride could be readily conjugated onto the polyols via ester linkages, forming HPG–NCTD conjugates. Owing to the coordination between cisplatin (CDDP) and the carboxyl groups in the HPG–NCTD conjugates, the nanoscale HPG–NCTD/CDDP complexes were obtained. Both in vitro and in vivo evaluations showed that the sequential release of CDDP and NCTD was achieved by the combination of coordination connections and hydrolysable ester bonds. Correspondingly, a synergistic efficiency of cancer treatment and immunity promotion was realized. These experimental results confirm that the sequential release of carriers based on coordination connections and degradable covalent bonds can be used to overcome the problems of leukopenia in cancer therapy, giving us a greater perspective in cancer treatment.