Toward high-stability quantitative carriers: development of superparamagnetic nanocarriers and a high-sensitivity mixing-frequency narrow-band magnetic particle imaging detection system

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Abstract
Introduction: Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted extensive attention in recent years as visualizable and controllable organic nanocarriers. Magnetic particle imaging (MPI), as a quantitative imaging method, enables visual and quantitative characterization of carriers. The quantitative imaging capability of carriers is critically crucial for precise quantitative local drug concentrations. However, the alternating current susceptibility (ACS) of SPIONs is highly susceptible to external interference and, thus, prone to fluctuations, which tend to be multifactorial and poorly defined in the in vivo environment, posing a major challenge to the quantitative analysis of carriers in living organisms. Methods: Through the analysis of the third-harmonic ACS of SPIONs, we proposed that under specific nanoscale dimensions and instrument frequency, the ACS maintained a relatively stable state, with a quantifiable fluctuation range even under complex interference conditions, thus enabling quantitative analysis in the in vivo environment. Meanwhile, to achieve precise detection of carriers with signal loss under the stability model, a novel high-sensitivity detection technique based on the narrow-band mixing-frequency theory was proposed. Results and Discussion: In vitro experiments demonstrated that only SPIONs with reduced core size and increased hydrodynamic diameter could exhibit relatively stable signals, consistent with the theoretical predictions, under strong interference environments. Further validation via a rabbit mammary sentinel lymph node (SLN) experiment demonstrated that the self-developed SPION carrier (with a core size of 20 nm and a hydrodynamic diameter of 80 nm) achieved long-term stable signal output in living animals, with its sensitivity reaching an acceptable level in the MPI detection system.

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