Superhydrophilic Fe^IV ₂Mn^II Nanocluster: A Combined Diagnostic and Therapeutic Agent

We report here an atomically precise nanocluster, (NH₄)₂Mn^II(H₂O)₂[Fe^IV(L)]₂·11H₂O (Fe₂Mn). This system was designed to harness superhydrophilic interactions to enhance magnetic resonance imaging (MRI), while permitting photoacoustic imaging (PAI) and photothermal antitumor therapy. It was synthesized using Fe-HDCL, an Fe(IV) system with strong near infrared (NIR) photothermal conversion capabilities, as a precursor and manganese(II) ion that allows for MRI as the metal center. Fe₂Mn not only produces a useful photothermal effect but also provides for MRI enhancement with a longitudinal relaxivity (r₁) of 7.67 mM^-1s^-1 at 0.5 T and 6.02 mM^-1s^-1 at 3.0 T, values that are nearly double those of common gadolinium-based contrast agents (e.g., Gd-DTPA, r₁ ≈ 3.0 ∼ 4.0 mM^-1s^-1). This enhanced relaxivity arises from two para-positioned water coordination sites (q = 2) on the manganese(II) ion and robust hydrogen bonding between hydrophilic groups on the Fe-HDCL surface and surrounding water molecules, forming a second-sphere hydration shell. As detailed below, the nanocluster of this study (Fe₂Mn) enables high-quality dual-mode MR/PA imaging and effective low-dose (25 µmol·kg^-1) laser-triggered photothermal tumor ablation. The present study thus demonstrates how rationally designed superhydrophilic architectures that control both inner sphere coordination and second sphere hydration dynamics can give rise to more effective theranostic agents.