A Supramolecular Crosslinker To Give Salt‐Resistant Polyion Complex Micelles and Improved MRI Contrast Agents

• Published in: Angewandte Chemie International Edition 2018-09, Vol.57 (39), p.12680-12684
• Main Authors: Wang, Jiahua, Wang, Junyou, Ding, Peng, Zhou, Wenjuan, Li, Yuehua, Drechsler, Markus, Guo, Xuhong, Cohen Stuart, Martien A.
• Format: Article
• Language: English
• Subjects: Biocompatibility; Cell Line, Tumor; Cell Survival - drug effects; Complex formation; Contrast agents; Contrast Media - chemistry; Contrast Media - toxicity; coordination polymers; Crosslinking; Disintegration; Electrostatic properties; Ferric Compounds - chemistry; Humans; Kidney - diagnostic imaging; Ligands; Liver; Liver - diagnostic imaging; Magnetic Resonance Imaging; Manganese - chemistry; Metal ions; Micelles; MRI contrast agents; Nanoparticles; Nanoparticles - chemistry; NMR; Nuclear magnetic resonance; Organs; polyelectrolytes micelles; Polymerization; Polymers - chemistry; Salts; Sodium Chloride - chemistry; Static Electricity; tunable stability and properties
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201805707

Three‐component mixtures (diblock copolymer/metal ion/oligoligand) can assemble into micellar particles owing to a combination of supramolecular polymerization and electrostatic complex formation. Such particles cover a large range of compositions, but the electrostatic forces keeping them together make them rather susceptible to disintegration by added salt. Now it is shown how the salt stability can be tuned continuously by employing both a bis‐ligand and a tris‐ligand, and varying the ratio of these in the mixture. For magnetic ions such as MnII and FeIII, the choice of the multiligand also affects the ion/water interaction and, hence, the magnetic relaxivity. As an example, MnII‐based nanoparticles with a very high longitudinal relaxivity (10.8 mm−1 s−1) were investigated that are not only biocompatible but also feature strong contrast enhancement in target organs (liver, kidney), as shown by T1‐weighted in vivo magnetic resonance imaging (MRI). Beating brine: Using two different DPA‐based oligo‐ligands (a bis‐ligand, L2 and tris‐ligand, L3) and metal ions, a supramolecular polyelectrolyte system was produced with cross‐links, the number of which can be varied by varying the L3/L2 ratio. Combining this with a charged‐neutral diblock copolymer led to M‐L2‐L3 micelles with tunable and enhanced salt stability and magnetic relaxivity that perform well as an MRI contrast agent.