Cycloacceleration of ferroptosis and calcicoptosis for magnetic resonance imaging-guided colorectal cancer therapy. (December 2022)

• Record Type: Journal Article
• Authors: Guo, Shuai; Li, Zongheng; Feng, Jie; Xiong, Wei; Yang, Jing; Lu, Xuanyi; Yang, Sugeun; Xu, Yikai; Wu, Aiguo; Shen, Zheyu
• Is Part Of: Nano today. Volume 47(2022)
• Publication Date: 2022-12
• Subjects: Colorectal cancer (CRC) therapy -- Ferroptosis -- Calcicoptosis -- Cycloacceleration -- Magnetic resonance imaging (MRI); Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101663
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: 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 H2 O2 and the high-level of endogenous H2 S 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 Fe 3+ /Ca 2+ (15.6 ± 3.4 % and 32.1 ± 1.9 %). The powerful T 1 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, H2 S 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. Graphical Abstract: A new concept of cycloacceleration of ferroptosis and calcicoptosis is proposed, and a new nanoplatform based on a superior magnetic resonance imaging (MRI) contrast agent with a superhigh r1 value (70.0 mM −1 s −1 ) and low r2 /r1 ratio (1.98) has been developed for MRI-guided colorectal cancer therapy based on the concept. ga1 Highlights: To develop a strategy for CRC theranostics, we propose a concept of cycloacceleration of ferroptosis and calcicoptosis. FGNP@TA-Fe/Ca realized cycloacceleration of ferroptosis and calcicoptosis for MRI-guided CRC therapy. The mechanism of cycloacceleration of ferroptosis and calcicoptosis was verified. The in vivo effectiveness and safety of FGNP@TA-Fe/Ca are demonstrated on the CT 26 tumor-bearing BALB/c mice.