Liposomal MRI probes containing encapsulated or amphiphilic Fe() coordination complexes

• Published in: Biomaterials science 2023-08, Vol.11 (17), p.5942-5954
• Main Authors: Chowdhury, Md Saiful I, Kras, Elizabeth A, Turowski, Steven G, Spernyak, Joseph A, Morrow, Janet R
• Format: Article
• Language: English
• Subjects: Blood circulation; Coordination compounds; Encapsulation; Iron; Liposomes; Micelles; Nanoparticles; Phosphonates; Protons
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/d3bm00029j

Liposomes containing high-spin Fe( iii ) coordination complexes were prepared towards the production of T 1 MRI probes with improved relaxivity. The amphiphilic Fe( iii ) complexes were anchored into the liposome with two alkyl chains to give a coordination sphere containing mixed amide and hydroxypropyl pendant groups. The encapsulated complex contains a macrocyclic ligand with three phosphonate pendants, [Fe(NOTP)] 3− , which was chosen for its good aqueous solubility. Four types of MRI probes were prepared including those with intraliposomal Fe( iii ) complex (LipoA) alone, amphiphilic Fe( iii ) complex (LipoB), both intraliposomal and amphiphilic complex (LipoC) or micelles formed with amphiphilic complex. Water proton relaxivities r 1 and r 2 were measured and compared to a small molecule macrocyclic Fe( iii ) complex containing similar donor groups. Micelles of the amphiphilic Fe( iii ) complex had proton relaxivity values ( r 1 = 2.6 mM −1 s −1 ) that were four times higher than the small hydrophilic analog. Liposomes with amphiphilic Fe( iii ) complex (LipoB) have a per iron relaxivity of 2.6 mM −1 s −1 at pH 7.2, 34 °C at 1.4 T whereas liposomes containing both amphiphilic and intraliposomal Fe( iii ) complexes (lipoC) have r 1 of 0.58 mM −1 s −1 on a per iron basis consistent with quenching of the interior Fe( iii ) complex relaxivity. Liposomes containing only encapsulated [Fe(NOTP)] 3− have a lowered r 1 of 0.65 mM −1 s −1 per iron complex. Studies show that the biodistribution and clearance of the different types liposomal nanoparticles differ greatly. LipoB is a blood pool agent with a long circulation time whereas lipoC is cleared more rapidly through both renal and hepatobiliary pathways. These clearance differences are consistent with lower stability of LipoC compared to LipoB. High spin Fe( iii ) centers in hydrophilic or amphiphilic complexes are incorporated into micelles or liposomes to form nanoparticle MRI probes. An amide pendant group linker incorporates the Fe( iii ) complexes into liposomes for studies in mice.