Single-Step Synthesis\nof Highly Sensitive <sup>19</sup>F MRI Tracers by Gradient Copolymerization-Induced\nSelf-Assembly

Amphiphilic gradient copolymers are promising alternatives\nto block\ncopolymers for self-assembled nanomaterials due to their straightforward\nsynthesis via statistical copolymerization of monomers with different\nreactivities and hydrophilicity. By carefully selecting monomers,\nnanoparticles can be synthesized in a single step through gradient\ncopolymerization-induced self-assembly (gPISA). We synthesized highly\nsensitive <sup>19</sup>F MRI nanotracers via aqueous dispersion gPISA\nof hydrophilic poly(ethylene glycol) methyl ether methacrylate (PEGMA)\nwith core-forming <i>N</i>,<i>N</i>-(2,2,2-trifluoroethyl)acrylamide\n(TFEAM). The PPEGMA-grad-PTFEAM nanoparticles were optimized to achieve\nspherical morphology and exceptional <sup>19</sup>F MRI performance.\nNoncytotoxicity was confirmed in Panc-1 cells. In vitro <sup>19</sup>F MR relaxometry and imaging demonstrated their diagnostic imaging\npotential. Notably, these gradient copolymer nanotracers outperformed\nblock copolymer analogs in <sup>19</sup>F MRI performance due to their\ngradient architecture, enhancing <sup>19</sup>F relaxivity. The synthetic\nversatility and superior <sup>19</sup>F MRI performance of gradient\ncopolymers highlight their potential in advanced diagnostic imaging\napplications.