The Positive Influence of Zinc Phthalocyanine on MRI Contrasts Helps Reducing Gadolinium Doses in Anticancer-MriTheranostics

Abstract

Bifunctional nanoparticles combining diagnostic and therapeutic functions (known as theranostic agents) are the subject of an increasing number of studies. This group includes liposomes - highly biocompatible spherical particles formed from lipids. Liposomes, after appropriate functionalization can be used as contrast agents in many imaging methods e.g. MRI (Magnetic Resonance Imaging). In addition, research on the properties of paramagnetic liposomes that contain a gadolinium (III) ion (Gd (III)) in their structure, as well as therapeutic agents, provide the basis for the preparation of a new generation of hybrid nanoparticles. These hybrids, due to their contrasting abilities in MRI, allow one to monitor the biodistribution of drugs administered in a human body. This study investigates changes in the 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 $\mathbf{r}_{1}s$ and $\mathbf{r}_{2}$ relaxivities. Here we demonstrate that the relaxation enhancement originates mainly from modification of a structure of the lipid bilayer. Modified Florence model was fitted to the experimental NMRD profiles of liposomal solutions (magnetic field range from 0.0002 T to 9.4 T). These results indicate the water permeability changes and deformation of the lipid bilayer structure as a result of ZnPc incorporation. 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. Therefore, increased water permeability results in an increase of the overall relaxivity. 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.