Fe 3+ @polyDOPA- b -polysarcosine, a T 1 -Weighted MRI Contrast Agent via Controlled NTA Polymerization.

α-Amino acid N -thiocarboxyanhydrides (NTAs) are promising cyclic monomers to synthesize polypeptides and polypeptoids via controlled ring-opening polymerizations. Superior to N -carboxyanhydrides requiring protection on hydroxyl groups, NTAs are able to tolerate such nucleophiles. In this work, we report the synthesis of NTA monomers containing unprotected phenolic hydroxyl groups of 3,4-dihydroxy-l-phenylalanine (DOPA) and l-tyrosine (Tyr). Their controlled ROPs and sequential copolymerizations with polysarcosine (PSar) yield PDOPA, PTyr, and PDOPA- b -polysarcosine (PDOPA- b -PSar) products quantitatively with designable degrees of polymerization. Micellar nanoparticles of Fe 3+ @PDOPA- b -PSar have been prepared thanks to the strong chelation of iron(III) cation by catechol ligands that act as T1-weighted magnetic resonance imaging (MRI) contrast agents. For instance, Fe 3+ @PDOPA 10 - b -PSar 50 exhibits higher longitudinal relaxivity ( r 1 = 5.6 mM -1 s -1 ) than commercial Gd 3+ -based compounds. Effective MRI contrast enhancement in vivo of nude mice with a moderate duration (150 min) and 3D magnetic resonance angiography in rabbit illustrated by using volume rendering and maximal intensity projection techniques ignite the clinical application of Fe 3+ -based polypept(o)ides in diagnostic radiology as Gd-free MRI contrast agents.