The Positive Influence of Therapeutic Agent on Relaxivities of Gadolinium-Loaded Liposomal Theranostics

This study investigates changes in the MRI contrast properties of Gd(III)-containing paramagnetic liposomes following the incorporation of photosensitizing agent (ZnPc—zinc phthalocyanine). It provides identification of mechanisms responsible for enhancement of proton relaxation rate and hence, the increased both r₁ and r₂ relaxivities. Five liposomal formulations, containing fatty acids derivatives of Gd(III) salt and hydrophobic ZnPc, were synthesized. NMRD profiles of liposomal solutions (magnetic field range from 0.0002 to 9.4 T) were obtained and Modified Florence model was applied. The contrast properties of the model drug itself was separated from the lipid bilayer deformation influence, caused by its incorporation. The latter resulted, among other, in optimization of an apparent water exchange correlation time. As Gd(III) is located in the outer and inner lipid layers, some of the Gd(III) chelates are localized in aqueous interior of the liposomes, thus their contrasting efficiency depends on the water exchange rate through the membrane. The proposed approach raises the possibility of reducing the amount of potentially harmful contrast media based on gadolinium, by taking into account the increase of the relaxation effect caused by other components of the system.