Multicore SPION Clustering within Poly(amino acid) Corrals for Enhanced MRI Contrast and Drug Release

Abstract Superparamagnetic iron oxide nanoparticle (SPION) clusters produce localized magnetic field inhomogeneities that enhance negative contrast in magnetic resonance imaging (MRI). It is shown that high transverse relaxivity ( r ₂ ) can be obtained by clustering hydrophobic SPIONs with an average core diameter of ≈7 nm via self‐assembly with amphiphilic polyethylene glycol‐ b ‐poly( L ‐Leucine) block copolymers, PEG _n ‐ b‐ p( L ‐Leu) _m , where the PEG chains are terminated by methoxy (CH ₃ O‐PEG _n ) or hydroxyl groups (HO‐PEG _n ). Clusters ranging from 65 to 85 nm in diameter are formed by polymer coating and stabilization of hydrophobic SPION aggregates and yield high r ₂ values ranging from 226 to 342 s ⁻¹ m m Fe ⁻¹ with negligible longitudinal relaxivity ( r ₁ ) and high saturation magnetization near that of bulk maghemite. Polymer composition determines the critical micelle concentrations, notably the length of the hydrophobic segment, and the extent of hydrophobic drug loading. However, it does not significantly impact the size of the SPION cluster assemblies, their magnetic relaxivity, or their drug release, whether passive or during pulsed, intermittent magnetic stimulation. This work demonstrates that the self‐assembled amphiphilic block copolymer‐based micelles can be used to enhance the colloidal and magnetic relaxivity behavior of SPION clusters while providing variable drug loading and the opportunity for end‐group functionalization.