Unleashing the Power of Magnetic Particle Imaging: Tailored Magnetic Nanoparticles for Ultrasensitive Detection of Bone Metastases in Prostate Cancer

Abstract Magnetic particle imaging (MPI) is a groundbreaking imaging technique hindered by suboptimal tracers, as current magnetic nanoparticles (MNPs) are primarily designed for magnetic resonance imaging and are not specifically tailored for the distinct physics of MPI. To address this issue, optimizing the magnetic diameter of MNPs is focused on, a pivotal parameter influenced by both physical size and magnetic disorder, yet underexplored in the development of MPI tracers. By employing a precise temperature‐controlled synthesis strategy, this study successfully modulates these parameters synergistically to create high‐performance Fe 310 P with an optimal magnetic diameter, exhibiting an eight‐fold increase in the MPI signal in vitro compared to the commercial tracer VivoTrax. Further surface functionalization with engineered macrophage membranes expressing a prostate‐specific membrane antigen (PSMA)‐targeting antibody fragment (gy‐1) yields tumor‐targeted Fe 310 4PM gy‐1 , which enables the detection of as few as 800 tumor cells with a single scan, without the need for repeated acquisitions. Compared to VivoTrax, Fe 310 4PM gy‐1 achieves a 330‐fold enhancement in the MPI signal in vivo, which enables the sensitive detection of prostate tumors and bone metastasis with 0.5 mm in diameter. This study provides valuable insights into the development of advanced MPI tracers, paving the way for broader biomedical applications of MPI.