Fe3+@polyDOPA-b-polysarcosine, a T1-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 Fe3+@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, Fe3+@PDOPA10-b-PSar50 exhibits higher longitudinal relaxivity (r1 = 5.6 mM-1 s-1) than commercial Gd3+-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 Fe3+-based polypept(o)ides in diagnostic radiology as Gd-free MRI contrast agents.