Coordination-driven self-assembled Mn(ii)-metallostar with high relaxivity and synergistic photothermal and photodynamic effects

A novel Mn(II)-metallostar structure (ML3Mn3, M = Fe3+, Ti4+) was synthesized through the self-assembly of high-valence transition-metal ions (Fe3+ and Ti4+) with a heteroditopic Mn(II) chelate (MnL) bearing a catechol group. UV-vis spectroscopy and variable-temperature 17O NMR reveals pH-dependent coordination modes of the FeL3Mn3 metallostar, with tris-coordination at pH 9.0 and an equilibrium between tris- and bis-coordination at pH 7.4. The heteropolymetallic Mn(II)-metallostars (ML3Mn3) demonstrated enhanced relaxivity per Mn (more than 2-fold) compared to the monomeric Mn(II) chelate (MnL). The Fe–Mn metallostar exhibited synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects upon 808 nm laser excitation due to ligand-to-metal charge transfer (LMCT) from the metal-catechol core, with a photothermal conversion efficiency of 20.3% and a singlet oxygen quantum yield of 24.8%. In vitro phototherapy studies showed that the Fe–Mn metallostar showed effective antitumor effects in the BxPC-3 cell line. In MRI studies in normal mice, low-dose FeL3Mn3 (25 μmol kg−1) provided a superior contrast-enhancement compared to Gd-DTPA (100 μmol kg−1) with rapid blood clearance and mixed hepatobiliary and renal excretion. In summary, we have developed a novel Mn(II)-metallostar structure with high relaxivities and synergistic NIR light-irritable PTT/PDT effects, which may be a promising theranostic agent for MRI-guided phototherapy.