Flash nanoprecipitation with Gd(III)-based metallosurfactants to fabricate polylactic acid nanoparticles as highly efficient contrast agents for magnetic resonance imaging.

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.