Macrocyclic gadolinium(iii) complexes with hyphenated-amino-N-oxide (HAO) type ligand structures are designed as efficient magnetic resonance imaging (MRI) contrast agents (CAs) with high relaxivity and stability.

Polydentate amine-N-oxide carboxylates were used as ligands for the formation of Gd(iii) complexes with high relaxivity as MRI contrast agents. Cytotoxicity assays revealed good cytocompatibility of these complexes for clinical applications.

Polylactic acid (PLA) nanoparticles coated with Gd(III)‐based metallosurfactants (MS) are prepared using a simple and rapid one‐step method, flash nanoprecipitation (FNP), for magnetic resonance imaging (MRI) applications. By co‐assembling the Gd(III)‐based MS and an amphiphilic polymer, methoxy poly(ethylene glycol)‐b‐poly(ϵ‐caprolactone) (mPEG‐b‐PCL), PLA cores were rapidly encapsulated to form biocompatible T1 contrast agents with tunable particle size and narrow size distribution. The hydrophobic property of Gd(III)‐based MS were finely tuned to achieve their high loading efficiency. The size of the nanoparticles was easily controlled by tuning the stream velocity, Reynolds number and the amount of the amphiphilic block copolymer during the FNP process. Under the optimized condition, the relaxivity of the nanoparticles was achieved up to 35.39 mM−1 s−1 (at 1.5 T), which is over 8 times of clinically used MRI contrast agents, demonstrating the potential application for MR imaging.

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/ppsc.202000044. Conformity of two biological imaging entities, magnetic resonance imaging (MRI) and fluorescence imaging, is achieved through co-assembly of a Gd(III)based metallosurfactant, conjugated polymeric nanoparticles, and amphiphilic block copolymer F127 (PEO 106 PPO 70 PEO 106 ) followed by crosslinking with organosilica. The cross-linked micelles with a size around 100 nm exhibit outstanding dispersion stability in aqueous and phosphate buffered saline solutions, bright fluorescence emission, and high relaxivities, providing a new approach to synthesize highly efficient bimodal contrast agents. The relaxivities of the co-assembled micelles are synergistically enhanced by incorporation of Gd(III) complexes with high hydration number (q = 3) and elongation of rotation correlation time to achieve r 1 values up to 105.37 mm −1 s −1 (at 1.5 T), which is over 20 times that of clinically used MRI contrast agents and among the highest values of all the nanoparticular MRI contrast agents. The external PEO layer endows these micelles with very low cytotoxicity for both in vitro and in vivo imaging. Meanwhile, thanks to the enhanced permeability and retention effect originating from their nanoscale sizes, the bimodal contrast agents show a prolonged blood circulation time in vivo and targeted accumulation at tumor regions to display outstanding MRI imaging performance. Scheme 1. Schematic illustration of the fabrication of the bimodal nanoparticular contrast agents.

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