Responsive Magnetic Particle Imaging Tracer: Overcoming “Always‐On” Limitation, Eliminating Interference, and Ensuring Safety in Adaptive Therapy

Abstract Magnetic particle imaging (MPI) has emerged as a novel technology utilizing superparamagnetic nanoparticles as tracers, essential for disease diagnosis and treatment guidance in preclinical animal models. Unlike other modalities, MPI provides high sensitivity, deep tissue penetration, and no signal attenuation. However, existing MPI tracers suffer from “always‐on” signals, which complicate organ‐specific imaging and hinder accuracy. To overcome these challenges, we have developed a responsive MPI tracer using pH‐responsive PdFe alloy particles coated with a gatekeeper polymer. This tracer exhibits pH‐sensitive Fe release and modulation of the MPI signal, enabling selective imaging with a higher signal‐to‐noise ratio and intratumoral pH quantification. Notably, this responsive tracer facilitates subtraction‐enhanced MPI imaging, effectively eliminating interference from liver uptake and expanding the scope of abdominal imaging. Additionally, the tracer employs a dual‐function mechanism for adaptive cancer therapy, combining pH‐switchable enzyme‐like catalysis with dual‐key co‐activation of ROS generation, and Pd skeleton that scavenges free radicals to minimize Fe‐related toxicity. This advancement promises to significantly expand MPI's applicability in diagnostics and therapeutic monitoring, marking a leap forward in imaging technology.