Nanoassemblies of the redox paclitaxel prodrug with the natural active ingredient dihydroartemisinin for therapy of breast cancer†
Abstract
Natural products have attracted attention owing to their multiple antitumor effects, improved chemotherapy sensitivity, and few side effects. The combination of natural active ingredients and chemotherapy drugs could be an effective strategy for synergistic antitumor therapy by preserving their activity to inhibit the growth of tumors, while reducing the side effects of chemotherapy drugs at relatively low doses. Although the feasibility of the delivery of natural products and chemotherapy drugs has been proven, most current carriers cannot be efficiently loaded, thus leading to a discrepancy in the drug release ratio compared to the predefined loading ratio. In this study, simple nanoassemblies with controllable drug release profiles were constructed to co-deliver paclitaxel (PTX) and dihydroartemisinin (DHA) for synergistic treatment of breast cancer. The nanoassemblies demonstrated a notable capacity for loading efficiency, micro-environmental triggering of drug release, and activation of the homodimeric prodrug at the tumor site, thereby facilitating successful combination therapy. The in vitro and in vivo antitumor effects were synergistically improved by combining DHA and PTX through prodrug modifications and nanoassemblies. Our findings provide a simple and efficient strategy for the development of nanoassemblies combining natural active ingredients with chemotherapeutic drugs.