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Dynamic changes in 1H-MR relaxometric properties of cell-internalized paramagnetic liposomes, as studied over a
Maarten B Kok1, Gustav J Strijkers, Klaas Nicolay
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Abstract:
Molecular imaging based on MRI requires the use of amplification strategies in order to achieve sufficient sensitivity for the detection of low-level molecular markers. Recently, we described a combination of two amplification methods: (i) the use of paramagnetic liposomes that can be prepared with a high payload of Gd(3+)-containing lipid; and (ii) targeting to a cell-surface receptor that can undergo multiple rounds of nanoparticle delivery in the cell, followed by recycling to the cell membrane. Liposome uptake was monitored over a period of 24 h and was found to lead to massive delivery in subcellular compartments. The present study aimed to monitor the longer-term fate of the cell-internalized contrast material by studying its relaxometric properties over 5 days, following an initial 24 h loading period. Circa 25% of the Gd(3+)-content delivered to the cells via integrin-targeted liposomes was lost in the first 24 h, which led to 65 and 77% reductions in R(1) and R(2), respectively, as compared with the original R(1) and R(2) enhancements. This implies that the remaining cell-associated gadolinium had relatively low effective r(1) and r(2) relaxivities. It is proposed that this is due to gradual release of Gd(3+) from the chelate in the cell, followed by sequestration in an MR silent state. Most of the gadolinium internalized by cells following incubation with non-targeted liposomes was released in the 5-day follow-up period.
Insights
Magnetic resonance imaging (MRI) needs amplification for detecting molecular markers. This study tracks gadolinium (Gd3+) liposomes in cells over 5 days, finding significant loss and reduced MRI signal, suggesting Gd3+ release.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Biochemistry
Background:
- MRI sensitivity is limited for detecting low-level molecular markers.
- Amplification strategies are crucial for enhancing MRI sensitivity.
- Paramagnetic liposomes and receptor-mediated endocytosis are promising amplification methods.
Purpose of the Study:
- To investigate the long-term fate of cell-internalized gadolinium (Gd3+)-containing liposomes.
- To evaluate the relaxometric properties of internalized contrast material over 5 days.
- To understand the stability and behavior of Gd3+ within cells after liposome delivery.
Main Methods:
- Utilized integrin-targeted paramagnetic liposomes with high Gd3+ payload.
- Monitored liposome uptake and intracellular delivery over 24 hours.
- Assessed relaxometric properties (R1 and R2) of internalized Gd3+ over a 5-day period.
Main Results:
- A significant loss of Gd3+ (approx. 25%) occurred within 24 hours post-delivery.
- Reductions in R1 (65%) and R2 (77%) enhancements were observed, indicating lower relaxivities.
- Gd3+ release from chelates and sequestration in an MR-silent state is proposed.
- Non-targeted liposomes showed substantial Gd3+ release over 5 days.
Conclusions:
- Cellular internalization of Gd3+-liposomes leads to substantial loss of contrast material and reduced MRI signal over time.
- The observed decrease in relaxivity suggests gradual Gd3+ release and sequestration within cells.
- These findings have implications for the design and application of liposomal contrast agents in molecular MRI.
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