LAUSR

Because of the insufficiency of hydrogen peroxide, the relatively low rate of Fenton reaction, and the active glutathione (GSH) peroxidase 4 (GPX4) in tumor cells, it is difficult to achieve a desirable efficacy of ferroptosis therapy (FT) for tumors based on nanomaterials. Inspired by the concept of "cyclotron" in physics, in this study, a new concept of cycloacceleration of reactive oxygen species (ROS) generation in tumor cells to realize high-performance FT of tumors is proposed. Typically, a magnetic resonance imaging (MRI) contrast agent of dotted core-shell Fe3 O4 /Gd2 O3 hybrid nanoparticles (FGNPs) is prepared based on exceedingly small magnetic iron oxide nanoparticles (ES-MIONs). Sorafenib (SFN) is loaded and poly(ethylene glycol) methyl ether-poly(propylene sulfide)-NH2 (mPEG-PPS-NH2 ) is grafted on the surface of FGNP to generate SA-SFN-FGNP via self-assembly. The results of in vitro and in vivo demonstrate SA-SFN-FGNP can work with the acidic tumor microenvironment and endosomal conditions, Fenton reaction and system XC - , and generate cyclic reactions in tumor cells, resulting in specific cycloacceleration of ROS generation for high-performance FT of tumors. The very high longitudinal relaxivity (r1 , 33.43 mM-1 s-1 , 3.0 T) makes sure that the SA-SFN-FGNP can be used for MRI-guided FT of tumors.