Recently, a significant research breakthrough was made by the research team led by Daishun Ling at Shanghai Jiao Tong University. Their work which is entitled " Ligand-mediated acid-activatable magnetic particle imaging probes for highly sensitive diagnosis of sepsis " has been officially published in the journal Matter.

Article abstract:

Progress and potential

Magnetic particle imaging (MPI) has demonstrated its versatility in various biomedical applications. However, most existing MPI imaging strategies are “always on” type, leading to background signal interference unrelated to pathological changes and limiting MPI application in monitoring molecular-level changes of disease-related biological processes. Our study addresses this challenge by designing imine bond-mediated acid responsive assemblies with tunable MPI performance, which employ tunable magnetic dipole interaction in the disassembling process and aims at unlocking principles for developing biomarker-responsive MPI strategies. In neutral medium, the short interparticle distance within the assembled structure of LAMPs maximizes the magnetic dipole interactions between the building blocks, which weakens the magnetization dynamics of LAMPs, thereby effectively quenching the MPI signal by restricting the BMCSs magnetic moments rotation. Conversely, in acidic conditions, the acid-labile imine bonds hydrolyze rapidly, restoring the MPI signal in a highly controlled, environment-dependent manner.

Improved acid-sensitive MPI performance can enable sensitive monitoring of the progression of septic disease characterized by a dynamic acidic microenvironment. This represents the first application of an acid-activatable MPI probe utilizing controlled nanometer-scale interparticle distances to modulate MPI signals for precise in vivo molecular imaging, providing a promising translational approach in the design of next-generation MPI tracers.

Highlights

•Rational building blocks and imine bonds construct robust acid-sensitive assemblies

•Interparticle distance modulates magnetic dipole interactions to tune MPI signals

•Acid-responsive MPI signal allows dynamic and precise molecular imaging for sepsis

Summary

Magnetic particle imaging (MPI) holds immense promise as a non-invasive biomedical imaging modality, but its advancement is hindered by the absence of activatable probes for biomarker-specific imaging. Here, we introduce a ligand-mediated acid-activatable MPI probe (LAMP) composed of magnetic nanoparticles linked via acid-sensitive imine bond-containing ligands. The LAMP exhibits stable assembly in neutral conditions and rapid disassembly in acidic microenvironments. The imine bond crosslinking promotes a compact structure that enhances magnetic dipole interactions, significantly quenching the initial MPI signal. Upon exposure to acidic conditions, the probe disassembles, restoring the MPI signal in a highly controlled, environment-dependent manner. This switchable assembly enables precise, real-time imaging of acidity-associated diseases such as sepsis progression. Our findings demonstrate that the ligand-mediated modulation of magnetic dipole interactions provides a versatile platform for the design of next-generation MPI probes for biomarker-specific MPI imaging.