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.

3rd Faculty of Medicine Charles University Ruská 87 100 00 Prague Czech Republic

Department of Diagnostic and Interventional Radiology Institute for Clinical and Experimental Medicine Videnska 1958 9 140 21 Prague Czech Republic

Department of Physical and Macromolecular Chemistry Faculty of Science Charles University 128 40 Prague 2 Czech Republic

Faculty of Health Studies Technical University of Liberec Studentská 1402 2 46117 Liberec Czech Republic

Institute of Biophysics and Informatics 1st Faculty of Medicine Charles University Kateřinská 1660 32 121 08 Prague Czech Republic

Institute of Macromolecular Chemistry v v i Academy of Sciences of the Czech Republic Heyrovsky Sq 2 162 06 Prague 6 Czech Republic

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