Biodegradable iron-coordinated hollow polydopamine nanospheres for dihydroartemisinin delivery and selectively enhanced therapy in tumor cells

As the semisynthetic derivative and active metabolite of the effective anti-malarial drug artemisinin, dihydroartemisinin (DHA) has been investigated as an emerging therapeutic agent for tumor treatment based on the cytotoxicity of free-radicals originating from interactions with ferrous ions. Meanwhile, simultaneously delivering DHA and iron ions to tumors for selectively killing cancer cells is still a great challenge in DHA tumor therapy. Herein, we develop a facile yet efficient strategy based on iron-coordinated hollow polydopamine nanospheres to load DHA (DHA@HPDA-Fe). The as-prepared nanoagent is biodegradable and exhibits controllable release of DHA and Fe ions in tumor microenvironments, resulting in ferrous ion-enhanced production of cytotoxic reactive oxygen species (ROS) by DHA and thus effectively killing the tumor cells. In vivo therapy experiments indicated that the anti-tumor efficacy of DHA@HPDA-Fe was about 3.05 times greater than that of free DHA, and the tumor inhibition ratio was 88.7% compared with the control group, accompanied by negligible side effects, indicating that the proposed nanomedicine platform is promising for anti-tumor applications. Biodegradable iron-coordinated hollow polydopamine nanospheres are successfully synthesized for dihydroartemisinin delivery and selectively enhanced therapy in tumor cells.