Peptide Materials Obtained by Aggregation of Polyphenylalanine Conjugates as Gadolinium‐Based Magnetic Resonance Imaging Contrast Agents

Abstract

Peptide materials based on the aggregation of poly-phenylalanine conjugates containing gadolinium complexes and acting as potential contrast agents (CAs) in Magnetic Resonance Imaging (MRI) are described. Monomers contain two (F2) or four (F4) phenylalanine residues for self-assembly, a chelating agent, DOTA or DTPA, for achieving gadolinium coordination and ethoxylic linkers at two (L2) or six (L6) PEG units between the chelating group and peptide region. Both DOTA and DTPA tetra-phenylalanine derivatives, and their gadolinium complexes DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4, are able to self-aggregate at very low concentration. Structural characterization, obtained by CD and IR measurements, confirms the amyloid type fibril formation in which an antiparallel peptide alignment is preferred. Amyloid type fibril formation was also observed, in solid state, by TEM images and X-ray diffraction patterns. The relaxivity values of DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4 and their ability to enhance the MRI cellular response on J774A.1 mouse macrophages cell line indicate that these peptide materials are promising candidate as a new class of supramolecular gadolinium based MRI contrast agents

Cross-beta nanostructures based on dinaphthylalanine Gd-conjugates loaded with doxorubicin

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In vivo membrane engineering traps Gd-based MRI contrast agents for detecting microhepatocellular carcinoma

“…This reaction immobilizes otherwise freely diffusing Gd chelates onto a rigid supramolecular scaffold, substantially prolonging the τ R (23). As a result, the assembled probe exhibits a markedly enhanced r 1 value (~15.51 mM -1 s -1 ), exceeding that of clinical Gd-DOTA by more than threefold, consistent with a previous study (45). SEM-EDX mapping confirmed homogeneous Gd distribution along the fibrillar scaffold, whereas VSM demonstrated that relaxivity enhancement arises from nanoscale confinement rather than altered paramagnetic properties.…”

Gadolinium containing telechelic PEG‐polymers end‐capped by di‐phenylalanine motives as potential supramolecular MRI contrast agents

“…Both compounds have been also fully characterized for their relaxometric properties and cell uptake and internalization in view of a potential use as MRI CAs. Even if the relaxometric parameters are in line with other examples of Gd(III) based supramolecular (micelles or liposomes) CAs , and more performing respect to classical low molecular weight CAs, the τ R values extracted from the fitting procedure are quite short if compared with those usually found for nano‐sized aggregates (1–30 ns) . The low τ R values we found can be attributed to the occurrence of a quite fast internal motility of the Gd‐complexes along the linker spacer with respect to the overall fibril‐like structures.…”