Single-Step Synthesis of Highly Sensitive ¹⁹F MRI Tracers by Gradient Copolymerization-Induced Self-Assembly

Amphiphilic gradient copolymers are promising alternatives to block copolymers for self-assembled nanomaterials due to their straightforward synthesis via statistical copolymerization of monomers with different reactivities and hydrophilicity. By carefully selecting monomers, nanoparticles can be synthesized in a single step through gradient copolymerization-induced self-assembly (gPISA). We synthesized highly sensitive ¹⁹F MRI nanotracers via aqueous dispersion gPISA of hydrophilic poly(ethylene glycol) methyl ether methacrylate (PEGMA) with core-forming N,N-(2,2,2-trifluoroethyl)acrylamide (TFEAM). The PPEGMA-grad-PTFEAM nanoparticles were optimized to achieve spherical morphology and exceptional ¹⁹F MRI performance. Noncytotoxicity was confirmed in Panc-1 cells. In vitro ¹⁹F MR relaxometry and imaging demonstrated their diagnostic imaging potential. Notably, these gradient copolymer nanotracers outperformed block copolymer analogs in ¹⁹F MRI performance due to their gradient architecture, enhancing ¹⁹F relaxivity. The synthetic versatility and superior ¹⁹F MRI performance of gradient copolymers highlight their potential in advanced diagnostic imaging applications.