Magneto-Liposomes as MRI Contrast Agents: A Systematic Study of Different Liposomal Formulations.

Nina Kostevšek,Wafa T Al-Jamal,Calvin C L Cheung,Igor Serša,Mauro Comes Franchini,Mateja Erdani Kreft,Ilaria Monaco,Janja Vidmar

doi:10.3390/nano10050889

Nina Kostevšek, Wafa T Al-Jamal + Show 6 more

Open Access

https://doi.org/10.3390/nano10050889

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Abstract

The majority of the clinically approved iron oxide nanoparticles (IO NPs) used as contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety concerns or lack of profits. To address this challenge, liposomes have been used to prepare IO-based T2 contrast agents. We studied the influence of different phospholipids on the relaxivity (r2) values of magneto-liposomes (MLs) containing magnetic NPs in the bilayer, where a strong correlation between the bilayer fluidity and r2 is clearly shown. Embedding 5-nm IO NPs in the lipid bilayer leads to a significant improvement in their relaxivity, where r2 values range from 153 ± 5 s−1 mM−1 for DPPC/cholesterol/DSPE-PEG (96/50/4) up to 673 ± 12 s−1 mM−1 for DOPC/DSPE-PEG (96/4), compared to “free” IO NPs with an r2 value of 16 s−1 mM−1, measured at 9.4 T MRI scanner. In vitro MRI measurements, together with the ICP-MS analysis, revealed MLs as highly selective contrast agents that were preferentially taken up by cancerous T24 cells, which led to an improvement in the contrast and an easier distinction between the healthy and the cancerous cells. A careful selection of the lipid bilayer to prepare MLs could offer efficient MRI contrast agents, even at very low IO NP concentrations.

Highlights

Magnetic resonance imaging (MRI) has good anatomic resolution and excellent soft-tissue contrast imaging capabilities
The synthesized oleic acid (OA)-coated iron oxide nanoparticles (IO NPs) were 4.5 ± 1 nm in diameter, as confirmed by the is shown in Figure 1b and indicates no structural changes and a good dispersion of NPs
The high uptake of hydrocaffeic acid (HCA)-IO NPs in both cell lines makes the differentiation between cancer and healthy cells relatively difficult. These results revealed that MLs could improve the contrast between the healthy and the cancerous tissues at lower Fe concentration than HCA-IO NPs, proving that MLs have a high potential as promising MRI contrast agents for in vivo applications

Summary

Introduction

Magnetic resonance imaging (MRI) has good anatomic resolution and excellent soft-tissue contrast imaging capabilities. A few have been marketed worldwide under the commercial names listed, where a list of all IO-based contrast agents with a description of the NP’s size, coating, and relaxivity values, together with the intended use and status on the market are shown. There is a need and a market space for novel IO NP-based imaging agents with a high safety margin and superior MRI properties. Liposomes are the most clinically approved nano-sized delivery systems [7], which proves their biocompatibility. Their structure allows the encapsulation of additional active components in their aqueous core, offering a great platform for the preparation of multifunctional nanoparticles for theranostics and image-guided drug delivery, including MRI imaging

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