Liposomal Fe(III) Macrocyclic Complexes with Hydroxypropyl Pendants as MRI Probes

Area of Science:

• Nanotechnology and Materials Science
• Biomedical Imaging and Contrast Agents
• Coordination Chemistry

Background:

• Development of novel paramagnetic contrast agents for Magnetic Resonance Imaging (MRI) is crucial for improved diagnostic capabilities.
• Iron(III) complexes offer potential as safer alternatives to gadolinium-based contrast agents due to lower toxicity.
• Liposomal formulations can enhance the delivery and performance of contrast agents.

Purpose of the Study:

• To prepare and characterize paramagnetic liposomes incorporating various iron(III) coordination complexes.
• To evaluate the relaxivity properties (T1 and T2) and MRI contrast enhancement capabilities of these novel liposomes.
• To compare the in vivo performance of iron(III)-loaded liposomes with a clinically used gadolinium contrast agent.

Main Methods:

• Synthesis of mononuclear (Fe(L1), Fe(L3)) and dinuclear (Fe2(L2)) iron(III) complexes with 1,4,7-triazacyclononane macrocycles.
• Preparation of two types of paramagnetic liposomes: LipoA (aqueous core loading) and LipoB (bilayer insertion and core loading).
• Characterization of liposomes using relaxivity measurements (r1, r2) across various magnetic field strengths and in vivo MRI studies in mice.

Main Results:

• Paramagnetic liposomes (LipoA, LipoB1, LipoB2) were successfully prepared, exhibiting enhanced T1 and T2 water proton relaxation rates.
• Liposomes with iron(III) complexes in the bilayer (LipoB1) showed unique spectral broadening under osmotic stress.
• Iron(III)-loaded liposomes demonstrated higher r1 relaxivity compared to LipoA, with stable performance across magnetic field strengths.
• In vivo MRI studies revealed prolonged blood contrast enhancement with LipoB1 compared to Gd(DOTA) at a higher dose.

Conclusions:

• Paramagnetic liposomes incorporating iron(III) complexes represent a promising new class of MRI contrast agents.
• The formulation strategy, particularly the incorporation of amphiphilic iron(III) complexes into the liposomal bilayer, significantly impacts relaxivity and in vivo performance.
• These iron(III)-based liposomes offer potential for improved and prolonged vascular imaging, potentially surpassing current gadolinium-based agents.