Design, synthesis and in vitro characterization of fluorescent and paramagnetic CXCR4-targeted imaging agents
Ole Tietz1, Nazila Kamaly, Graham Smith
1Department of Surgery and Cancer, Comprehensive Cancer Imaging Centre, Hammersmith Hospital, Imperial College London London, W12 0NN, UK.
Abstract:
The G-protein coupled C-X-C chemokine receptor type 4 (CXCR4) is highly overexpressed in a range of cancers and is therefore an excellent biomarker for cancer imaging. To this end targeted iron oxide nanoparticles were developed and utilised for in vitro imaging of MDA-MB-231 breast cancer cells overexpressing the CXCR4 receptor. Nanoparticles comprising an iron oxide core, encapsulated in a stabilising epichlorohydrin crossed-linked dextran polymer, were conjugated to a cyclopentapeptide with affinity to the CXCR4 receptor. The particles were characterized for their size, surface charge and r2 relaxivity at 4.7 T. MR imaging of the CXCR4 receptor with targeted iron oxide nanoparticles revealed an approximately 3-fold increase in T2 signal enhancement of MDA-MB-231 cells compared to non-targeted controls. Prussian blue staining of labeled MDA-MB-231 cells revealed darker and more intense staining of the cellular membrane. This study demonstrates the potential of targeted iron oxide nanoparticles for the imaging of the CXCR4 receptor by magnetic resonance imaging (MRI).
Insights
Targeted iron oxide nanoparticles show promise for cancer imaging. These nanoparticles, designed to bind the CXCR4 receptor, enhanced MRI signals in breast cancer cells, demonstrating their potential for improved diagnostics.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Medical Imaging
Background:
- C-X-C chemokine receptor type 4 (CXCR4) is overexpressed in various cancers, making it a valuable biomarker.
- Targeted nanoparticles offer potential for specific cancer cell detection and imaging.
Purpose of the Study:
- To develop and evaluate targeted iron oxide nanoparticles for in vitro imaging of CXCR4-overexpressing breast cancer cells.
- To assess the efficacy of these nanoparticles in enhancing magnetic resonance imaging (MRI) contrast.
Main Methods:
- Iron oxide nanoparticles were synthesized with a dextran polymer coating and conjugated to a CXCR4-targeting cyclopentapeptide.
- Particle characterization included size, surface charge, and r2 relaxivity measurements.
- In vitro MRI was performed on MDA-MB-231 breast cancer cells, with and without targeted nanoparticles.
Main Results:
- Targeted nanoparticles demonstrated approximately a 3-fold increase in T2 signal enhancement in MDA-MB-231 cells compared to non-targeted controls.
- Prussian blue staining confirmed intense labeling on the cellular membrane of targeted cells.
- Characterization confirmed particle properties suitable for MRI applications.
Conclusions:
- Targeted iron oxide nanoparticles show significant potential for enhancing MRI-based imaging of the CXCR4 receptor.
- This approach could lead to improved diagnostic capabilities for CXCR4-positive cancers.
- Further development may enable in vivo applications for cancer detection and monitoring.
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