Abstract
Developing novel nanomedicines based on clinically approved agents has emerged as a promising anticancer therapeutic strategy. Nevertheless, the tailored optimization of clinically approved Prussian blue (PB) via Zn doping has yet to attract sufficient attention, particularly its capacity to intervene in the tumor microenvironment. Herein, we employed doping engineering to modulate the structural and functional properties of PB nanoparticles (NPs), with results revealing that zinc doping possessed intrinsic advantages over Co and Mn in narrowing size distribution and generating ultrasmall nanostructures. In addition, these ultrasmall Zn-doped PB NPs displayed outstanding tumor theranostic performance, featuring boosted enzyme-mimetic catalytic activity, favorable MRI imaging capacity, and diverse bioactivities. By catalyzing H2O2 substrates and regulating endogenous molecular pools, they could remodel the breast tumor microenvironment and trigger apoptosis and ferroptosis. This study offers new inspirations for the rational design of metal-doped nanomaterials and delivers valuable strategies to optimize clinically approved therapeutic agents.