Cycloacceleration of ferroptosis and calcicoptosis for magnetic resonance imaging-guided colorectal cancer therapy

Ferroptosis therapy (FT) of the colorectal cancer (CRC) is usually restricted by the relatively slow rate of Fenton reaction due to the limited concentration of intracellular H2O2 and the high-level of endogenous H2S with strong reducibility. To develop an unprecedented strategy for precise targeted CRC theranostics, inspired by the “cyclotron” concept in physics, we propose a new concept of cycloacceleration of ferroptosis and calcicoptosis for the magnetic resonance imaging (MRI)-guided CRC therapy. The developed FGNPs@TA-Fe3/Ca4 nanoparticles have an ideal hydrodynamic diameter of 16.5 ± 2.2 nm and relatively high loading contents of Fe3+/Ca2+ (15.6 ± 3.4 % and 32.1 ± 1.9 %). The powerful T1 imaging ability of FGNPs@TA-Fe3/Ca4 with TME-responsive relaxivities is identified by 7.0 and 3.0 T of MRI scanners. The cycloacceleration of ferroptosis and calcicoptosis induced by FGNPs@TA-Fe3/Ca4 is reinforced by the MTT assay, and the measurements of reactive oxygen species (ROS), lipid peroxide (LPO), glutathione (GSH) peroxidase 4 (GPX4) bioactivity, GSH, H2S and SO2 of CT 26 cells with various treatments with or without ferroptosis or calcicoptosis inhibitors. The in vivo effectiveness and safety of FGNPs@TA-Fe3/Ca4 for MRI-guided CRC therapy based on cycloacceleration of ferroptosis and calcicoptosis are demonstrated on the CT 26 tumor-bearing BALB/c mice.