(603g) Cross-Linkable Magnetic Nanocluster Tracers: A Triblock Copolymer Approach for Magnetic Particle Imaging

Magnetic Particle Imaging (MPI) is an emerging tomographic modality that visualizes the spatial distribution of superparamagnetic iron oxide nanoparticles (SPIONs) in tissues. SPIONs have been studied as promising tracers for MPI applications due to the magnetic moments that saturate at low magnetic fields at tens of milliteslas (mT) with higher clinical safety margins. Our goal is to develop a multifunctional platform with high magnetic field response capable of co-encapsulating other therapeutic materials. This is achieved using a series of amphiphilic HO-PEG₇₇-AG₁₀-p(L-Leu)_m and HO-PEG₁₁₃-AG₁₀-p(L-Leu)_m tri-block copolymers synthesized with varying hydrophobic chain lengths with Leu repeat units (m) between 6-60 to form self-assembled cross-linkable micelles loaded with hydrophobic SPIONs with core diameter 5 nm. While SPIONs alone exhibited weak magnetic responses, when clustered within the micelle core, they collectively responded to the field while retaining their superparamagnetic behavior. The particle size of the SPION-loaded micelles before cross-linking ranged from 74 ± 1 nm to 189 ± 9 nm, while after cross-linking, the size increased from 143 ± 25 nm to 220 ± 7 nm. TEM images revealed clustered SPIONs within the micellar core, with interparticle surface spacing controlled by the ligands and hydrophobic PAA blocks. In this study, we utilized the Brownian relaxation dynamics of SPIONs using a magnetic particle spectroscopy (MPS) platform to quantitatively detect cellular uptake. Herein, the findings provided valuable insights into understanding how the molecular weight of the hydrophilic moiety and hydrophobic chain length affect the magnetic performance of SPIONs clusters as MPI tracer.