Breaking the Trade-off in MPI-Guided Magnetic Hyperthermia by Tailoring the Dynamic Magnetization of Magnetic Nanoparticles via Site-Selective Trace Doping.

Among various theranostic strategies, magnetic particle imaging-guided magnetic hyperthermia therapy (MPI-MHT) stands out for its ability to provide real-time, quantitative imaging alongside controlled tumor ablation. Nevertheless, its advancement is hindered by the conflicting requirements for dynamic magnetization of magnetic nanoparticles (MNPs), which are crucial for optimizing both the MPI signal and the efficacy of MHT. This complexity makes it challenging to enhance performance synergistically within a single agent. Herein, we present an innovative site-selective doping strategy using trace amounts of cobalt to tailor the dynamic magnetization of MNPs, specifically optimizing key parameters including dynamic susceptibility and relaxation time. The resulting trace cobalt-doped nanoparticles (TCMPs) achieve a 7.4-fold enhancement in the MPI signal and a 12-fold increase in the specific absorption rate for heating compared to the commercial tracer VivoTrax. Furthermore, by engineering TCMPs with genetically modified cell membranes, we fabricate a prostate cancer-targeted MPI-MHT agent, TCMPs@CM, which enables effective visualization and ablation of both subcutaneous and postsurgical residual tumors in mouse models. This study introduces a novel paradigm for the development of high-performance MPI-MHT platforms, demonstrating significant potential for advancing precision cancer theranostics.