Controlled Synthesis of the FeB Nanometallic Glasses with Stronger Electron Donating Capability to Activate Molecular Oxygen for the Enhanced Ferroptosis Therapy.

Abstract

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.