Considering the strong electron-donating ability and the superior biocompatibility, the integration of zero-valent iron nanostructure Fe0 (electron-reservoir) and zero-valent boron nanostructure B0 offers great promise for fabricating novel ferroptosis nanoagents. Nevertheless, the controlled and facile synthesis of alloyed Fe0 and B0 nanostructure-FeB nanometallic glasses (NMGs) has remained a long-standing challenge. Herein, a complexion-reduction strategy is proposed for the controlled synthesis of FeB NMGs with greater electron donating capacity to activate the molecular oxygen for improved ferroptosis therapy. In-depth mechanism reveales that the complexion-reduction strategy effectively prevent the long-range diffusion of Fe0, resulting in the amorphous alloyed Fe0 and B0 nanostructure-FeB nanoparticles (FeB NPs). The FeB NPs display stronger electron donating capability and electron transfer rate 9.4 times higher than that of the Fe0 NPs, which effectively activate the molecular oxygen to produce ∙O2 -, H2O2 and ∙OH. The in vitro cellular experiments confirm the FeB-ss-SiO₂ NPs (encapsulation with SiO2 outlayer containing -S-S- bonds) demonstrates the enhanced ferroptosis. The tumor-bearing mice models shows that FeB-ss-SiO₂ NPs exhibited superior biocompatibility and tumor inhibition effect (inhibition rate of 73%), which improve the overall survival rate for 30 days post-treatment. This study will provide an innovative way to design therapeutic nanoagents for cancer treatments.
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