Development of Anticancer Ferric Complex Based on Human Serum Albumin Nanoparticles That Generate Oxygen in Cells to Overcome Hypoxia-Induced Resistance in Metal Chemotherapy.

To achieve the remarkable therapeutic efficacy of a ferric (Fe) complex via a reactive oxygen species (ROS) mechanism in solid tumors, a therapeutic Fe-based Schiff-base complex ( Fe1 ) was synthesized and encapsulated in human serum albumin (HSA) nanoparticles (NPs), which generated oxygen (O2 ) in cancer cells in situ. The HSA-Fe1-O 2 NP ( HSA-Fe1-O 2 NP ) delivery system effectively overcame hypoxia-induced resistance in metal chemotherapy, alleviated the hypoxic condition of tumor tissues, and showed excellent tumor suppression by generating excess ROS and promoting the apoptosis of SK-N-MC tumor cells. The HSA-Fe1-O 2 NPs not only enhanced the ability of the Fe1 complex to target tumor cells but also decreased adverse effects in vivo.