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–O2 NP (HSA–Fe1–O2NP) 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–O2NPs not only enhanced the ability of the Fe1 complex to target tumor cells but also decreased adverse effects in vivo.