Co-Assembly of Gd(III)-Based Metallosurfactant and Conjugated Polymer Nanoparticles in Organosilica Cross-Linked Block Copolymer Micelles for Highly Efficient MRI and Fluorescent Bimodal Imaging

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 (PEO₁₀₆PPO₇₀PEO₁₀₆) 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 r₁ 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.